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Biomedical subjects

B Chang

Publications and source records attributed to B Chang.

At least 55 records · Page 3Linked to original sources
PubMed2000

The bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularization.

Ocular neovascularization is the leading cause of blindness in developed countries and often causes rapid loss of vision in age-related macular degeneration. Acute visual loss is most often due to hemorrhage from new vessels that have extended from the choroid into the subretinal space. Growth of abnormal vessels beneath the retina in this condition is known as subretinal neovascularization (SRN). Age-related animal models of macular degeneration and SRN have not been described. Current animal models of SRN depend on chemical or physical stimuli to initiate growth of subretinal vessels. The genes responsible for age-related human macular degeneration with SRN have not been firmly identified. We report an angiogenic phenotype in Bst/+ mice that is age-related, clinically evident, and resembles human SRN. This represents a spontaneous, genetically determined model of SRN. Bst/+ mice offer the possibility of exploring the molecular mechanisms of SRN without the need for exogenous agents.

Aging↗
PubMed2000

Lop12, a mutation in mouse Crygd causing lens opacity similar to human Coppock cataract.

A new cataract mutation was discovered in an ongoing program to identify new mouse models of hereditary eye disease. Lens opacity 12 (Lop12) is a semidominant mutation that results in an irregular nuclear lens opacity similar to the human Coppock cataract. Lop12 is associated with a small nonrecombining segment that maps to mouse Chromosome 1 close to the eye lens obsolescence mutation (Cryge(Cat2-Elo)), a member of the gamma-crystallin gene cluster (Cryg). Using a systemic candidate gene approach to analyze the entire Cryg cluster, a G to A transition was found in exon 3 of Crygd associated with the Lop12 mutation and has been designated Crygd(Lop12). The mutation Crygd(Lop12) leads to the formation of an in-frame stop codon that produces a truncated protein of 156 amino acids. It is predicted that the defective gene product alters protein folding of the gamma-crystallin(s) and results in lens opacity.

Animals↗
PubMed2000

Translational control of ribosomal protein L4 mRNA is required for rapid neurite regeneration.

Under some circumstances neurons can be primed to rapidly regenerate injured neuritic processes independent of new gene expression. Such transcription-independent neurite extension occurs in adult rat sensory neurons cultured after sciatic nerve crush and in NGF-differentiated PC12 cells whose neurites have been mechanically sheared. In the PC12 cells, neurite regeneration occurs by means of translational control of mRNAs which were transcribed prior to neurite injury. The survival of such translationally regulated mRNAs is relatively short in the differentiated PC12 cells (< or =10 h). By subtractive hybridization, we have isolated a short-lived mRNA from differentiated PC12 cells. This mRNA, which encodes the ribosomal protein L4, is translationally regulated during neurite regeneration in PC12 cells. Antisense oligonucleotides to L4 mRNA inhibit neurite regeneration from the differentiated PC12 cells as well as axonal elongation from conditioned sensory neurons, indicating that ongoing translation of L4 mRNA is needed for these forms of rapid transcription-independent neurite growth. Taken together, these data point to the importance of translational regulation of existing neuronal mRNAs in the regenerative responses to neuronal injury. Although there are other examples of neuronal translational control, there are no other known neuronal proteins whose levels are regulated predominantly by translational rather than transcriptional control.

Animals↗
PubMed2000

Acute annular outer retinopathy: report of four cases.

PURPOSE: To describe the clinical findings and course in four patients with acute annular outer retinopathy. METHODS: Four patients were evaluated during the course of acute annular outer retinopathy, and the historical and clinical findings were retrospectively collected. RESULTS: Four healthy patients developed the acute onset of visual field loss associated with a localized, white annular outer retinopathy. All patients were caucasian; two were women, aged 29 and 32 years, and two were men, aged 71 and 79 years. The mean follow-up was 3.9 years (range, 1 to 6 years). On presentation, four eyes had an irregular, incomplete, peripapillary, annular band of gray-white, deep retinal opacification with visual CONCLUSIONS: These four cases of acute annular outer retinopathy expand our knowledge of this disorder. Acute annular outer retinopathy may be a distinct entity or it may represent a variant of acute zonal occult outer retinopathy retinopathy. As more cases are recognized, the characteristic features of the disease spectrum, the etiology, and treatment options may be better elucidated.

Acute Disease↗
PubMed2000

Extensor tendon rupture after internal fixation of a distal radius fracture using a dorsally placed AO/ASIF titanium pi plate. Arbeitsgemeinschaft für Osteosynthesefragen/Association for the Study of Internal Fixation.

Extensor tenosynovitis has been reported as a complication of the Arbeitsgemeinschaft für Osteosynthesefragen/Association for the Study of Internal Fixation (AO/ASIF) pi plate. The authors present a case of extensor tendon rupture after internal fixation with a pi plate after one of the screws in the distal limb loosened. This mechanism of extensor tendon rupture has not been reported previously. With appropriate prevention, monitoring, and intervention this complication could have been avoided. Schnur DP, Chang B. Extensor tendon rupture after internal fixation of a distal radius fracture using a dorsally placed AO/ASIF titanium pi plate.

Bone Plates↗
PubMed2000

Limb salvage of lower-extremity wounds using free gracilis muscle reconstruction.

An extensive series reviewing the benefits and drawbacks of use of the gracilis muscle in lower-extremity trauma has not previously been collected. In this series of 50 patients, the use of microvascular free transfer of the gracilis muscle for lower-extremity salvage in acute traumatic wounds and posttraumatic chronic wounds is reviewed. In addition, the wound size, injury patterns, problems, and results unique to the use of the gracilis as a donor muscle for lower-extremity reconstruction are identified. In a 7-year period from 1991 to 1998, 50 patients underwent lower-extremity reconstruction using microvascular free gracilis transfer at the University of Maryland Shock Trauma Center, Johns Hopkins Hospital, and Johns Hopkins Bayview Medical Center. There were 22 patients who underwent reconstruction for coverage of acute lower-extremity traumatic soft-tissue defects associated with open fractures. The majority of patients were victims of high-energy injuries with 91 percent involving motor vehicle or motorcycle accidents, gunshot wounds, or pedestrians struck by vehicles. Ninety-one percent of the injuries were Gustilo type IIIb tibial fractures and 9 percent were Gustilo type IIIc. The mean soft-tissue defect size was 92.2 cm2. Successful limb salvage was achieved in 95 percent of patients. Twenty-eight patients with previous Gustilo type IIIb tibia-fibula fractures presented with posttraumatic chronic wounds characterized by osteomyelitis or deep soft-tissue infection. Successful free-tissue transfer was accomplished in 26 of 28 patients (93 percent). All but one of the patients in this group who underwent successful limb salvage (26 of 27, or 96 percent) are now free of infection. Use of the gracilis muscle as a free-tissue transfer has been shown to be a reliable and predictable tool in lower-extremity reconstruction, with a flap success and limb salvage rate comparable to those in other large studies.

Accidents, Traffic↗
PubMed2000

Rotation of the clavicular portion of the pectoralis major for soft-tissue coverage of the clavicle. An anatomical study and case report.

BACKGROUND: The purposes of this study were to describe the anatomical features of a rotational flap consisting of the clavicular portion of the pectoralis major and to report the surgical technique and the outcome of use of this flap in a patient with poor soft-tissue coverage following multiple operations for a clavicular fracture complicated by nonunion and infection. METHODS: Ten shoulders from five cadavera were dissected to isolate the clavicular portion of the pectoralis major. The vascular pedicle, thoracoacromial artery, and axillary artery were identified, and the length of the vascular pedicle from the axillary artery to the muscle was measured. The angle of rotation of the flap about its intact clavicular origin was measured before and after division of the acromial branch of the thoracoacromial artery. The clavicular origin was then incised, and the overall length, width, and thickness of the muscle as well as the distance from each end of the muscle to the vascular pedicle were measured. RESULTS: The average length of the vascular pedicle from the axillary artery to the pectoralis muscle belly was 5.3 centimeters (range, 3.7 to 6.5 centimeters). The average maximum angle of rotation with the clavicular origin intact was 60 degrees (range, 55 to 67 degrees) before division of the acromial branch and 73 degrees (range, 65 to 82 degrees) after division. The average total length of the clavicular head was 20.2 centimeters (range, 18.0 to 23.0 centimeters). The average width of the clavicular head was 2.9 centimeters (range, 2.0 to 4.0 centimeters), and the average thickness was 0.5 centimeter (range, 0.2 to 0.7 centimeter). The vascular pedicle entered the muscle an average of 8.7 centimeters (range, 5.2 to 10.7 centimeters) lateral to the most medial extent of the muscle and an average of 11.5 centimeters (range, 9.5 to 14.0 centimeters) medial to the most lateral extent of the muscle. The rotational flap was successfully used clinically to provide soft-tissue coverage after bone-grafting and internal fixation of a clavicular nonunion that had been complicated by infection. CONCLUSIONS: The clavicular head of the pectoralis major may be used as a local rotational flap to cover soft-tissue deficiencies over the clavicle. It can be harvested with relative ease without damaging the sternocostal head.

Aged↗
PubMed2000

Retinal degeneration 6 (rd6): a new mouse model for human retinitis punctata albescens.

PURPOSE: To characterize the genetics and phenotype of a new mouse mutant with retinal degeneration, rd6, that is associated with extensive, scattered, small white retinal dots seen ophthalmoscopically. METHODS: The phenotype was characterized using ophthalmoscopy, fundus photography, electroretinography, light microscopy, immunocytochemistry, and electron microscopy. Genetic characterization and linkage analysis studies were performed using standard methods. RESULTS: The inheritance pattern of rd6 is autosomal recessive. Linkage analysis mapped rd6 to mouse Chromosome 9 approximately 24 cM from the centromere, suggesting that the human homolog may be on chromosome 11q23. Ophthalmoscopic examination of mice homozygous for rd6 revealed discrete subretinal spots oriented in a regular pattern across the retina. The retinal spots appeared by 8 to 10 weeks of age and persisted through advanced stages of retinal degeneration. Histologic examination revealed large cells in the subretinal space, typically juxtaposed to the retinal pigment epithelium. The white dots seen on fundus examination corresponded both in distribution and size to these large cells. By 3 months of age, the cells were filled with membranous profiles, lipofuscin-like material, and pigment. These cells reacted strongly with an antibody directed against a mouse macrophage-associated antigen. Photoreceptor cells progressively degenerated with age, and an abnormal electroretinogram was initially detected between 1 and 2 months of age. CONCLUSIONS: The fundi of mice homozygous for rd6 exhibit phenotypic similarities to the human flecked retinal disorder retinitis punctata albescens. Thus, rd6/rd6 mice may be a model for understanding the etiology of this or similar disorders. The relationship between the aberrant subretinal cells and the concomitant photoreceptor degeneration remains to be established.

Animals↗
PubMed2000

[Isolation and identification of HN-98 strain of spotted fever group rickettsiae].

OBJECTIVE: One strain of rickettsiae was isolated from a patient with unknown fever from Qiongzhong county in Hainan Province in 1998, using embryonated hen eggs and proved to be the member of rickettsiae by the methods of morphology. It was named HS-98 strain after the name of the place and the year it was isolated. METHODS: The isolate was identified by methods of Microcomplement fixation assay and OCR/RFLP and compared with known species and strains of SFGR by DNA polymerase chain reaction and DNA polymerase chainreaction and was followed by restriction endonuclease fragment length polymorphism analysis. RESULTS: Results demonstrated that HN-98 strain was antigenically and genotypically identical to R. sibirica 246. CONCLUSION: The results suggested that there existed natural foci of spotted fever in Qiongzhong Area of Hainan Province.

Adult↗
PubMed1999

Functional and structural diversity of the human Dickkopf gene family.

Wnt proteins influence many aspects of embryonic development, and their activity is regulated by several secreted antagonists, including the Xenopus Dickkopf-1 (xDkk-1) protein. xDkk-1 inhibits Wnt activities in Xenopus embryos and may play a role in induction of head structures. Here, we characterize a family of human Dkk-related genes composed of Dkk-1, Dkk-2, Dkk-3, and Dkk-4, together with a unique Dkk-3 related protein termed Soggy (Sgy). hDkks 1-4 contain two distinct cysteine-rich domains in which the positions of 10 cysteine residues are highly conserved between family members. Sgy is a novel secreted protein related to Dkk-3 but which lacks the cysteine-rich domains. Members of the Dkk-related family display unique patterns of mRNA expression in human and mouse tissues, and are secreted when expressed in 293T cells. Furthermore, secreted hDkk-2 and hDkk-4 undergo proteolytic processing which results in cleavage of the second cysteine-rich domain from the full-length protein. Members of the human Dkk-related family differ not only in their structures and expression patterns, but also in their abilities to inhibit Wnt signaling. hDkk-1 and hDkk-4, but not hDkk-2, hDkk-3 or Sgy, suppress Wnt-induced secondary axis induction in Xenopus embryos. hDkk-1 and hDkk-4 do not block axis induction triggered either by Xenopus Dishevelled (Xdsh) or Xenopus Frizzled-8 (Xfz8), both of which function to transduce signals from Wnt ligands. Thus, hDkks 1 and 4 may inhibit Wnt activity by a mechanism upstream of Frizzled. Our findings highlight the structural and functional heterogeneity of human Dkk-related proteins.

Amino Acid Sequence↗
PubMed1999

Mouse fundus photography and angiography: a catalogue of normal and mutant phenotypes.

PURPOSE: Mice are an increasingly important tool in ophthalmic research. As a result of studying spontaneous and induced mutations, many new ocular diseases have been described in mice in recent years, including several degenerative retinal diseases that demonstrate progression with age. Clearly, documentation of progressive changes in clinical phenotype is an important facet of characterizing new mutations and for comparing them with human diseases. Despite these facts, there are few published photographs of mouse fundi. The small size of the mouse eye and the steep curvature of its structures have made it difficult to obtain high quality fundus photographs. The purpose of this work was to develop procedures for mouse fundus photography and angiography and to use these techniques to examine several new mouse strains with ocular abnormalities. METHODS: We have used a small animal fundus camera and condensing lens to develop a reliable technique for producing high quality fundus images of conscious albino and pigmented mice. The fundus camera also was utilized to develop a method for fluorescein angiography, which demonstrated the normal retinal vascular bed as well as abnormal vascular leakage. In addition, several mouse strains with previously unreported ocular abnormalities (including two with inherited optic nerve colobomas) and a catalogue of previously unpublished clinical images for various mutant mice are presented. RESULTS: Altogether, we provide clinical images for C57BL/6J, BALB/cByJ, retinal degeneration 1 (rd1), Rd2, rd3, rd7, achondroplasia, nervous, motor neuron degeneration, Purkinje cell degeneration, kidney and retinal defects, optic nerve coloboma 1, and two apparently multigenic optic nerve colobomas in a strain of mixed derivation (ONC) and the inbred CALB/Rk strain. CONCLUSIONS: Our photography procedure reliably produces high quality images of the mouse fundus. This permitted us to record progressive retinal changes over time in the same animal, allowed us to compare the phenotypes of newly discovered retinal mutants to existing mutants at other institutions and to potentially similar human conditions, and finally, permitted us to produce a catalogue of previously unpublished clinical phenotypes for various mutant mice.

Animals↗
PubMed1999

Identification of a missense mutation in the alphaA-crystallin gene of the lop18 mouse.

PURPOSE: The mouse lop18 (lens opacity 18) mutation causes a white cataract obvious at weaning age. It soon progresses to a large white nuclear cataract with mild cortical changes. The mutation maps to mouse Chromosome 17 in close linkage to the alphaA-crystallin (Crya) gene, which encodes one of the major vertebrate eye lens proteins. Here we report the identification of a missense mutation in the alphaA-crystallin gene of lop18/lop18 mutant mice. METHODS: PCR primers were designed based on the alphaA-crystallin gene sequence from GenBank and PCR products were sequenced. RESULTS: We have analysed the sequence of the alphaA-crystallin gene from the lop18/lop18 mouse and identified a missense mutation. This mutation is tightly associated with the cataract phenotype, as no recombination was detected in 112 meioses. CONCLUSIONS: Our results suggest that a missense mutation in the alphaA-crystallin gene is responsible for the lop18/lop18 phenotype and Cryalop18 should be used as a gene symbol for the lop18 mutation.

Animals↗
PubMed1999

Chromosomal localization of the loci responsible for dystrophic cardiac calcinosis in DBA/2 mice.

Dystrophic cardiac calcinosis (DCC) occurs in certain inbred strains of mice, including DBA/2 and C3H/He, and is generally found as an incidental lesion in adult animals at necropsy. Preliminary genetic studies into the cause of DCC have been performed in DBA/2 mice and suggest that DCC is inherited as an autosomal recessive trait involving three or four unlinked genes. To investigate the genetics of DCC further, we produced myocardial cell death by freeze-thaw injury to induce DCC. Experiments were conducted with three F1 hybrids made using three inbred strains of mice (DBA/2J and C3H/HeJ, DCC-susceptible strains; C57BL/6J, DCC-resistant strain) to compare the genetic factors in the development of DCC. We found that DBA/2 and C3H/He mice share the same gene pattern(s) that is responsible for DCC. We determined by backcross linkage analysis in DBA/2 and C57BL/6 mice that at least one recessive locus is responsible for DCC. A haplotype analysis of the backcross data demonstrated that the recessive locus, designated dyscalc1, is located on Chromosome 7, 20.5 cM distal to the centromere. The likely candidate genes for dyscalc1 are discussed. Further understanding of the structure and function of these mutant genes will be beneficial in explaining the molecular pathogenesis of DCC.

Animals↗
PubMed1999

The functional role of positively charged amino acid side chains in alpha-bungarotoxin revealed by site-directed mutagenesis of a His-tagged recombinant alpha-bungarotoxin.

A polyhistidine tag was added to the N-terminus of alpha-bungarotoxin (Bgtx) recombinantly expressed in E. coli. The His-tagged Bgtx was identical to native, venom-derived Bgtx in its apparent affinity for the nicotinic acetylcholine receptor (nAChR) in Torpedo electric organ membranes. Furthermore, in a physiological assay involving mouse muscle nAChR expressed in Xenopus oocytes, the His-tagged Bgtx was as effective as authentic Bgtx at blocking acetylcholine-evoked currents. Ala-substitution mutagenesis of His-tagged Bgtx was used to evaluate the functional contribution of Arg36, a residue that is invariant among all alpha-neurotoxins. Replacement with Ala resulted in a 90-fold decrease in the apparent affinity for the Torpedo nAChR and a corresponding 150-fold increase in the IC50 for block of heterologously expressed mouse muscle nAChR, demonstrating the critical importance of this positive charge for the binding and functional activity of a long alpha-neurotoxin. The observed decrease in affinity corresponds to a DeltaDeltaG of 2.7 kcal/mol and indicates that Arg36 makes a major contribution to complex formation. This finding is consistent with the proposal that Arg36 mimics the positive charge found on acetylcholine and directs the toxin to interact with receptor sites normally involved in acetylcholine recognition. In comparison, Ala-substitution of the highly conserved Lys26 resulted in only a 9-fold decrease in apparent affinity. Truncation of the His-tagged Bgtx following residue 67 produces a toxin lacking the seven C-terminal residues including the two positively charged residues Lys70 and Arg72. Truncation leads to a 7-fold decrease in apparent binding affinity.

Amino Acid Substitution↗
PubMed1999

Hydrogen bonding between sugar and protein is responsible for inhibition of dehydration-induced protein unfolding.

The nature of the interaction responsible for the inhibition of protein unfolding and subsequent damage by sugars during dehydration is unclear. The relationship between sample moisture content measured by coulometric Karl Fischer titration and the apparent moisture content predicted by the area of the protein side chain carboxylate band at approximately 1580 cm-1 in infrared spectra of dried protein-sugar samples was examined. For samples in which a high level of native protein structure was retained in the dried solid, the apparent moisture content predicted by the carboxylate band area was greater than the actual moisture content, indicating that protection results from direct sugar-protein hydrogen bonding and not entrapment of water at the protein surface. Further, we show that the degree of structural protection conferred by sucrose and trehalose apparent in second derivative, amide I infrared spectra, correlates with the extent of hydrogen bonding between sugar and protein. The failure of dextran to inhibit dehydration-induced lysozyme unfolding is shown to result from the inability of the polymer to hydrogen bond adequately to the protein. Therefore, formation of an amorphous phase alone is not sufficient to maintain protein structure during dehydration. Glucose hydrogen bonds to a high degree with dried lysozyme, but is incapable of inhibiting lyophilization-induced protein unfolding in the absence of an effective cryoprotectant. However, the addition of polyethylene glycol, which is known to protect proteins during freezing, but not drying, to glucose protected lysozyme structure during lyophilization. Together, these results show that hydrogen bonding between carbohydrate and protein is necessary to prevent dehydration-induced protein damage. However, hydrogen bonding alone is not sufficient to protect proteins during lyophilization in the absence of adequate freezing protection.

Animals↗
PubMed1999

Experimental fetal vesicoureteral reflux induces renal tubular and glomerular damage, and is associated with persistent bladder instability.

PURPOSE: We assessed renal function and urodynamic status in animals with experimental congenital vesicoureteral reflux. MATERIALS AND METHODS: Vesicoureteral reflux was surgically induced in male sheep fetuses at 95 days of gestation. After birth the animals were maintained on antibiotic prophylaxis. At ages 1 week and 6 months reflux was assessed by fluoroscopic voiding cystography. Cystometrography was performed with the animals awake. Serum creatinine, inulin clearance and the excretion of urinary N-acetyl-beta-D-glucosaminidase were measured at ages 1 week, 1 month and 6 months by surveillance urine cultures. Urinary concentrating capacity was assessed by desmopressin testing at ages 1 and 6 months. RESULTS: Nine animals (18 renal units) were born after the induction of reflux. There was no reflux in 2 renal units, while reflux was mild in 2, moderate in 5 and severe in 9. In the 6 animals available for followup at age 6 months only severe reflux persisted. Reflux resolution was associated with normalization of bladder urodynamics. Surveillance urine cultures were negative until age 6 months, when infection developed in 3 of the 6 lambs. In all animals serum creatinine was normal during followup. Glomerular filtration rate in the lambs with reflux was no different from normal at age 1 week but it was significantly less than normal independent of infection at age 6 months (2.7 versus 3.9 ml./kg. per minute, p = 0.002). As an indicator of renal tubular injury the ratio of N-acetyl-beta-D-glucosaminidase-to-creatinine remained significantly higher in animals with reflux than in normal animals from ages 1 week to 6 months (51.0 versus 10.2 IU/mg., p = 0.03). Maximal concentrating ability after desmopressin testing was already less than normal by age 1 month with a maximal increase of 98 versus 435 mOsm./l. in lambs with reflux versus normal lambs (p <0.0001). It was further impaired by age 6 months. Urodynamic evaluation of the animals with reflux revealed decreased bladder compliance at age 1 week with normal voiding pressure. In addition, in those with reflux there was a more pronounced immature voiding pattern with multiple phasic contractions due to sphincteric activity as well as a post-void bladder contraction. CONCLUSIONS: Our model of fetal vesicoureteral reflux induces alterations in renal function that are consistent with clinical observations and marked by altered tubular function but a relatively mild decrease in glomerular filtration. Bladder dynamics are altered, consistent with observations in human neonates with high grade reflux and bladder instability. Whether this represents cause or effect remains unclear. Our model permits focused study of the interaction of these factors in neonatal reflux and may allow the application of more specific therapies, particularly those directed toward mechanisms of renal and bladder dysfunction.

Animals↗
PubMed1999

Interacting loci cause severe iris atrophy and glaucoma in DBA/2J mice.

Glaucomas are a major cause of blindness. Visual loss typically involves retinal ganglion cell death and optic nerve atrophy subsequent to a pathologic elevation of intraocular pressure (IOP). Some human glaucomas are associated with anterior segment abnormalities such as pigment dispersion syndrome (PDS) and iris atrophy with associated synechiae. The primary causes of these abnormalities are unknown, and their aetiology is poorly understood. We recently characterized a mouse strain (DBA/2J) that develops glaucoma subsequent to anterior segment changes including pigment dispersion and iris atrophy. Using crosses between mouse strains DBA/2J (D2) and C57BL/6J (B6), we now show there are two chromosomal regions that contribute to the anterior segment changes and glaucoma. Progeny homozygous for the D2 allele of one locus on chromosome 6 (called ipd) develop an iris pigment dispersion phenotype similar to human PDS. ipd resides on a region of mouse chromosome 6 with conserved synteny to a region of human chromosome 7q that is associated with human PDS. Progeny homozygous for the D2 allele of a different locus on chromosome 4 (called isa) develop an iris stromal atrophy phenotype (ISA). The Tyrpl gene is a candidate for isa and likely causes ISA via a mechanism involving pigment production. Progeny homozygous for the D2 alleles of both ipd and isa develop an earlier onset and more severe disease involving pigment dispersion and iris stromal atrophy.

Age Factors↗