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Judy Savige - One of the best experts on this subject based on the ideXlab platform.
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ocular features in alport syndrome pathogenesis and clinical significance
Clinical Journal of The American Society of Nephrology, 2015Co-Authors: Deb Colville, Shivanand Sheth, Anjali Nicholson, Heather G Mack, Judy Savige, Anita LeysAbstract:Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Mutations in the COL4A5 (X-linked), or COL4A3 and COL4A4 (autosomal recessive) genes result in absence of the collagen IV α3α4α5 network from the basement membranes of the cornea, lens capsule, and retina and are associated with corneal opacities, anterior Lenticonus, fleck retinopathy, and temporal retinal thinning. Typically, these features do not affect vision or, in the case of Lenticonus, are correctable. In contrast, the rarer ophthalmic complications of posterior polymorphous corneal dystrophy, giant macular hole, and maculopathy all produce visual loss. Many of the ocular features of Alport syndrome are common, easily recognizable, and thus, helpful diagnostically, and in identifying the likelihood of early-onset renal failure. Lenticonus and central fleck retinopathy strongly suggest the diagnosis of Alport syndrome and are associated with renal failure before the age of 30 years, in males with X-linked disease. Sometimes, ophthalmic features suggest the mode of inheritance. A peripheral retinopathy in the mother of a male with hematuria suggests X-linked inheritance, and central retinopathy or Lenticonus in a female means that recessive disease is likely. Ocular examination, retinal photography, and optical coherence tomography are widely available, safe, fast, inexpensive, and acceptable to patients. Ocular examination is particularly helpful in the diagnosis of Alport syndrome when genetic testing is not readily available or the results are inconclusive. It also detects complications, such as macular hole, for which new treatments are emerging.
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Clinical and genetic features in autosomal recessive and X-linked Alport syndrome
Pediatric Nephrology, 2014Co-Authors: Yan Yan Wang, Deb Colville, Vanessa Sivakumar, Mardhiah Mohammad, Helen Storey, Frances Flinter, Hayat Dagher, Judy SavigeAbstract:Background This study determined the family history and clinical features that suggested autosomal recessive rather than X-linked Alport syndrome. Methods All patients had the diagnosis of Alport syndrome and the mode of inheritance confirmed by genetic testing, and underwent examination at a single centre. Results Patients comprised 9 males and 6 females with autosomal recessive Alport syndrome, and 18 males and 22 females with X-linked disease. Fourteen (93 %) individuals with autosomal recessive Alport syndrome developed early end-stage renal failure, all 15 had hearing loss, and most had Lenticonus (12, 80 %), and a central (13, 87 %) or peripheral (13, 87 %) retinopathy. These features occurred as often as in males with X-linked disease. Females with autosomal recessive inheritance were less likely to have an affected family member in another generation ( p = 0.01) than females with X-linked disease. They were more likely to have renal failure ( p = 0.003), hearing loss ( p = 0.02) and Lenticonus ( p
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The retinal "lozenge" or "dull macular reflex" in Alport syndrome may be associated with a severe retinopathy and early-onset renal failure.
The British journal of ophthalmology, 2008Co-Authors: Deb Colville, Yan Yan Wang, Rachel B. Tan, Judy SavigeAbstract:Background and aims: Alport syndrome is an inherited disease with renal failure, and often a hearing loss, Lenticonus and dot-and-fleck retinopathy. A retinal “lozenge” or “dull macular reflex” has been described in some patients. This study determined the prevalence and significance of this sign. Methods: Twenty-three patients from 14 families with X linked Alport syndrome and seven from four families with autosomal recessive disease underwent slit-lamp biomicroscopy for Lenticonus, direct and indirect ophthalmoscopy, and photography for the retinopathy. Results: The lozenge was present in five males (38%) but no females with X linked Alport syndrome, as well as one individual with recessive disease (1/7, 14%). It resulted from the sharp demarcation between the normal fovea and a perifoveal annnulus of confluent dots and flecks that were obvious with magnification of retinal photographs. The lozenge was first noted in adolescence and was always associated with early-onset renal failure, hearing loss and Lenticonus. Conclusion: Clinicians must be aware that the “lozenge” or “dull macular reflex” described in Alport syndrome is not a normal variant but reflects a severe, almost confluent perimacular dot and fleck retinopathy. This sign is useful diagnostically and also prognostically, since it is associated with early-onset renal failure.
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The use of ocular abnormalities to diagnose X-linked Alport syndrome in children
Pediatric Nephrology, 2008Co-Authors: Ke Wei Zhang, Deb Colville, Rachel Tan, Colin Jones, Stephen I. Alexander, Jeffrey Fletcher, Judy SavigeAbstract:The diagnosis of X-linked Alport syndrome is often difficult, but the demonstration of Lenticonus and retinopathy may facilitate the diagnosis in adult patients. The aim of this study was to determine the diagnostic usefulness of ocular examination in children. Fourteen families with at least one affected child were studied clinically, and COL4A5 mutations were determined. The families included 15 affected boys (median age 11 years, range 4–19 years). Two boys (13%) had renal failure, nine (60%) had a known hearing loss, one (7%) had Lenticonus and five (33%) had a central (4/15, 27%) or peripheral (4/14, 29%) retinopathy. Lenticonus and retinopathy were first noted in 14 and 11 year olds, respectively. All boys with retinopathy had a hearing loss. The early onset retinopathy was associated with a severe mutation (Q1383X). Eight families (8/14, 57%) comprised only sons and mothers, and two mothers (2/12, 17%) had the retinopathy. Six boys (40%) would have been diagnosed with Alport syndrome on the basis of their own or their mother’s ocular examinations. None of the six girls (median age 8 years, range 7–14 years) had ocular abnormalities. Hearing loss is usually highly sensitive for the diagnosis of Alport syndrome, but ocular examination of boys and their mothers at the initial consultation is a non-invasive test that is helpful in up to 40% cases.
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Absence of ocular manifestations in autosomal dominant Alport syndrome associated with haematological abnormalties.
Ophthalmic genetics, 2000Co-Authors: Deb Colville, Yan Yan Wang, R. Jamieson, F. Collins, Jeni Hood, Judy SavigeAbstract:Most patients with Alport syndrome have X-linked or autosomal recessive disease that is characterised by renal failure, hearing loss, and, in nearly 75% of the cases, a dot-and-fleck retinopathy and anterior Lenticonus. There are only case reports of individuals with the rare autosomal dominant form, who can have haematuria or renal failure, deafness, and, in addition, low platelet counts and neutrophil inclusions. The ocular features of autosomal dominant inheritance have not been described. We have examined the eyes in the members of two families where Alport syndrome was diagnosed on the basis of the clinical features and family history, and where autosomal dominant inheritance was confirmed by father-to-son disease transmission, the associated haematological abnormalities, and haplotypes that segregated with the recently described locus at chromosome 22q. In Family A, the eyes of two individuals with haematuria, hearing loss, and haematological abnormalities and of nine unaffected family members were examined. In Family B, the eyes of two individuals with renal failure, normal hearing, and haematological abnormalities were examined. None of the affected or unaffected members in either family had a dot-and-fleck retinopathy, anterior Lenticonus, a history suggesting recurrent corneal erosions, or corneal dystrophy. These results indicate that the protein abnormality in autosomal dominant Alport syndrome does not produce the retinopathy and Lenticonus typical of X-linked and autosomal recessive disease. This may be because the abnormal protein is not present or is less important in the ocular basement membranes than elsewhere, or because the presence of a normal allele in autosomal dominant disease compensates for the defective allele.
Deb Colville - One of the best experts on this subject based on the ideXlab platform.
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ocular features in alport syndrome pathogenesis and clinical significance
Clinical Journal of The American Society of Nephrology, 2015Co-Authors: Deb Colville, Shivanand Sheth, Anjali Nicholson, Heather G Mack, Judy Savige, Anita LeysAbstract:Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Mutations in the COL4A5 (X-linked), or COL4A3 and COL4A4 (autosomal recessive) genes result in absence of the collagen IV α3α4α5 network from the basement membranes of the cornea, lens capsule, and retina and are associated with corneal opacities, anterior Lenticonus, fleck retinopathy, and temporal retinal thinning. Typically, these features do not affect vision or, in the case of Lenticonus, are correctable. In contrast, the rarer ophthalmic complications of posterior polymorphous corneal dystrophy, giant macular hole, and maculopathy all produce visual loss. Many of the ocular features of Alport syndrome are common, easily recognizable, and thus, helpful diagnostically, and in identifying the likelihood of early-onset renal failure. Lenticonus and central fleck retinopathy strongly suggest the diagnosis of Alport syndrome and are associated with renal failure before the age of 30 years, in males with X-linked disease. Sometimes, ophthalmic features suggest the mode of inheritance. A peripheral retinopathy in the mother of a male with hematuria suggests X-linked inheritance, and central retinopathy or Lenticonus in a female means that recessive disease is likely. Ocular examination, retinal photography, and optical coherence tomography are widely available, safe, fast, inexpensive, and acceptable to patients. Ocular examination is particularly helpful in the diagnosis of Alport syndrome when genetic testing is not readily available or the results are inconclusive. It also detects complications, such as macular hole, for which new treatments are emerging.
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Clinical and genetic features in autosomal recessive and X-linked Alport syndrome
Pediatric Nephrology, 2014Co-Authors: Yan Yan Wang, Deb Colville, Vanessa Sivakumar, Mardhiah Mohammad, Helen Storey, Frances Flinter, Hayat Dagher, Judy SavigeAbstract:Background This study determined the family history and clinical features that suggested autosomal recessive rather than X-linked Alport syndrome. Methods All patients had the diagnosis of Alport syndrome and the mode of inheritance confirmed by genetic testing, and underwent examination at a single centre. Results Patients comprised 9 males and 6 females with autosomal recessive Alport syndrome, and 18 males and 22 females with X-linked disease. Fourteen (93 %) individuals with autosomal recessive Alport syndrome developed early end-stage renal failure, all 15 had hearing loss, and most had Lenticonus (12, 80 %), and a central (13, 87 %) or peripheral (13, 87 %) retinopathy. These features occurred as often as in males with X-linked disease. Females with autosomal recessive inheritance were less likely to have an affected family member in another generation ( p = 0.01) than females with X-linked disease. They were more likely to have renal failure ( p = 0.003), hearing loss ( p = 0.02) and Lenticonus ( p
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The retinal "lozenge" or "dull macular reflex" in Alport syndrome may be associated with a severe retinopathy and early-onset renal failure.
The British journal of ophthalmology, 2008Co-Authors: Deb Colville, Yan Yan Wang, Rachel B. Tan, Judy SavigeAbstract:Background and aims: Alport syndrome is an inherited disease with renal failure, and often a hearing loss, Lenticonus and dot-and-fleck retinopathy. A retinal “lozenge” or “dull macular reflex” has been described in some patients. This study determined the prevalence and significance of this sign. Methods: Twenty-three patients from 14 families with X linked Alport syndrome and seven from four families with autosomal recessive disease underwent slit-lamp biomicroscopy for Lenticonus, direct and indirect ophthalmoscopy, and photography for the retinopathy. Results: The lozenge was present in five males (38%) but no females with X linked Alport syndrome, as well as one individual with recessive disease (1/7, 14%). It resulted from the sharp demarcation between the normal fovea and a perifoveal annnulus of confluent dots and flecks that were obvious with magnification of retinal photographs. The lozenge was first noted in adolescence and was always associated with early-onset renal failure, hearing loss and Lenticonus. Conclusion: Clinicians must be aware that the “lozenge” or “dull macular reflex” described in Alport syndrome is not a normal variant but reflects a severe, almost confluent perimacular dot and fleck retinopathy. This sign is useful diagnostically and also prognostically, since it is associated with early-onset renal failure.
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The use of ocular abnormalities to diagnose X-linked Alport syndrome in children
Pediatric Nephrology, 2008Co-Authors: Ke Wei Zhang, Deb Colville, Rachel Tan, Colin Jones, Stephen I. Alexander, Jeffrey Fletcher, Judy SavigeAbstract:The diagnosis of X-linked Alport syndrome is often difficult, but the demonstration of Lenticonus and retinopathy may facilitate the diagnosis in adult patients. The aim of this study was to determine the diagnostic usefulness of ocular examination in children. Fourteen families with at least one affected child were studied clinically, and COL4A5 mutations were determined. The families included 15 affected boys (median age 11 years, range 4–19 years). Two boys (13%) had renal failure, nine (60%) had a known hearing loss, one (7%) had Lenticonus and five (33%) had a central (4/15, 27%) or peripheral (4/14, 29%) retinopathy. Lenticonus and retinopathy were first noted in 14 and 11 year olds, respectively. All boys with retinopathy had a hearing loss. The early onset retinopathy was associated with a severe mutation (Q1383X). Eight families (8/14, 57%) comprised only sons and mothers, and two mothers (2/12, 17%) had the retinopathy. Six boys (40%) would have been diagnosed with Alport syndrome on the basis of their own or their mother’s ocular examinations. None of the six girls (median age 8 years, range 7–14 years) had ocular abnormalities. Hearing loss is usually highly sensitive for the diagnosis of Alport syndrome, but ocular examination of boys and their mothers at the initial consultation is a non-invasive test that is helpful in up to 40% cases.
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Absence of ocular manifestations in autosomal dominant Alport syndrome associated with haematological abnormalties.
Ophthalmic genetics, 2000Co-Authors: Deb Colville, Yan Yan Wang, R. Jamieson, F. Collins, Jeni Hood, Judy SavigeAbstract:Most patients with Alport syndrome have X-linked or autosomal recessive disease that is characterised by renal failure, hearing loss, and, in nearly 75% of the cases, a dot-and-fleck retinopathy and anterior Lenticonus. There are only case reports of individuals with the rare autosomal dominant form, who can have haematuria or renal failure, deafness, and, in addition, low platelet counts and neutrophil inclusions. The ocular features of autosomal dominant inheritance have not been described. We have examined the eyes in the members of two families where Alport syndrome was diagnosed on the basis of the clinical features and family history, and where autosomal dominant inheritance was confirmed by father-to-son disease transmission, the associated haematological abnormalities, and haplotypes that segregated with the recently described locus at chromosome 22q. In Family A, the eyes of two individuals with haematuria, hearing loss, and haematological abnormalities and of nine unaffected family members were examined. In Family B, the eyes of two individuals with renal failure, normal hearing, and haematological abnormalities were examined. None of the affected or unaffected members in either family had a dot-and-fleck retinopathy, anterior Lenticonus, a history suggesting recurrent corneal erosions, or corneal dystrophy. These results indicate that the protein abnormality in autosomal dominant Alport syndrome does not produce the retinopathy and Lenticonus typical of X-linked and autosomal recessive disease. This may be because the abnormal protein is not present or is less important in the ocular basement membranes than elsewhere, or because the presence of a normal allele in autosomal dominant disease compensates for the defective allele.
David S. Chu - One of the best experts on this subject based on the ideXlab platform.
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Wavefront analysis and Scheimpflug imagery in diagnosis of anterior Lenticonus.
Journal of cataract and refractive surgery, 2010Co-Authors: Peter S. Hersh, David S. ChuAbstract:We present the case of an Alport syndrome patient whose anterior Lenticonus was detected by wavefront analysis and Scheimpflug imaging technology. The patient's lenticular abnormalities were too subtle to be detected by the initial slitlamp examination. Normal corneal topography and elevation maps with high total-eye aberrations pointed to internal optics as the source of aberrations, and predominant negative spherical aberrations suggested anterior Lenticonus, a diagnosis confirmed by Scheimpflug images that showed central bulging of the anterior lens surface. Following diagnosis, uneventful phacoemulsification and intraocular lens implantation were performed. We recommend wavefront analysis and Scheimpflug imaging technology as effective tools in the detection of lens disorders, especially those that are too subtle to be observed by other examination methods.
Shikha Gupta - One of the best experts on this subject based on the ideXlab platform.
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Wavefront analysis to diagnose blunt trauma-induced Weigert ligament dialysis: Isolated peripheral posterior Lenticonus.
Journal of cataract and refractive surgery, 2018Co-Authors: Arjun Desai, Mrinalini A. Yadav, Viney Gupta, Shikha GuptaAbstract:A 15-year-old male patient presented with vision loss after blunt trauma to the right eye and with clinical evidence of posterior Lenticonus. The posttraumatic Lenticonus was eccentric (superotemporal). Irregular astigmatism with high myopia on dilated retinoscopy within the Lenticonus, localized posterior convexity of peripheral capsule on ultrasound biomicroscopy, and increased higher-order aberrations (HOAs) on wavefront aberrometry compared with fellow-eye findings confirmed the diagnosis. To our knowledge, acquired peripheral posterior Lenticonus representing dialysis of Weigert ligament after acute blunt trauma is a new finding. This case provides an insight into the pattern of higher HOAs associated with any type of Lenticonus.
Michael A. Bearn - One of the best experts on this subject based on the ideXlab platform.
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Surgical identification of posterior Lenticonus.
Journal of cataract and refractive surgery, 2002Co-Authors: Thandalam S. Kalyanasundaram, Michael A. BearnAbstract:A 79-year-old patient was referred for cataract and high myopia. His optometrist noted difficult refraction. Biometry predicted an emmetropic intraocular lens power of +22.0 diopters. During cataract extraction, the typical features of posterior Lenticonus were noted. A careful look for posterior Lenticonus is suggested in cases in which there is a discrepancy between the biometry and refraction and no significant nuclear sclerosis to account for the high myopia. Surgeons should be aware of dehiscence or thinning of the posterior capsule while doing cataract extraction in these patients.