Evidence of retinal degeneration in Wolfram syndrome

Purpose: Wolfram syndrome is characterized by early onset diabetes mellitus, diabetes insipidus, deafness, and optic atrophy, but retinal degeneration has not been described as a major component of the phenotype. We present two cases with Wolfram syndrome and evidence of retinal degeneration.

Materials and Methods: Observational case series. Patients underwent complete ocular examinations as well as retinal imaging and electroretinography.

Results: Both patients had electroretinographic evidence of retinal dysfunction/degeneration in addition to optic atrophy with an otherwise normal-appearing retina.

Conclusions: Some patients with Wolfram syndrome have a mild retinal degeneration that may be a manifestation of the neuronal involvement that is present in this condition.     

Genetic Testing for Wolfram Syndrome Mutations in a Sample of 71 Patients with Hereditary Optic Neuropathy and Negative Genetic Test Results for OPA1/OPA3/LHON

In this study, the authors present a sample of 71 patients with hereditary optic neuropathy and negative genetic test results for OPA1/OPA3/LHON. All of these patients later underwent genetic testing to rule out WFS. As a result, 53 patients (74.7%) were negative and 18 patients (25.3%) were positive for some type of mutation or variation in the WFS gene. The authors believe that this study is interesting because it shows that a sizeable percentage (25.3%) of patients with hereditary optic 25 neuropathy and negative genetic test results for OPA1/OPA3/LHON had WFS mutations or variants.     

Wolfram syndrome: A clinical study of two cases

Two unrelated patients with two different images of Wolfram (or DIDMOAD) syndrome are presented: a 19—year old woman suffering from all the important features of this syndrome, and a 38—year old man showing two major characteristics but several minor abnormalities. This syndrome should be considered in young diabetic patients with unexplained visual loss or with polyuria and polydipsia in the presence of adequate blood sugar control. An early diagnosis is important to prevent unnecessary diagnostic investigations.     

Evidence for genetic heterogeneity in families with congenital motor nystagmus (CN)

Background: Wolfram syndrome is characterized by optic atrophy, insulin dependent diabetes mellitus, diabetes insipidus and deafness. There are several other associated conditions reported in the literature, but congenital or early childhood cataracts are not among them.

Materials and methods: Observational case series with confirmatory genetic analysis.

Results: A pair of siblings, followed over 17 years, who manifest congenital or early childhood cataracts, diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. They are both compound heterozygotes for mutations (V415 deletion and A684V substitution) in the WFS1 gene. Their father has congenital sensorineural hearing loss and developed optic atrophy. He is heterozygous for A684V in WFS1.

Conclusions: Wolfram syndrome should be in the differential diagnosis of genetic syndromes associated with congenital and early childhood cataracts. Here, we report on a mother who is a phenotypically normal carrier of an autosomal recessive Wolfram syndrome gene, and a father who has some of the findings of the syndrome and carries a single mutation that appears to be responsible for his hearing loss and optic atrophy. Their 2 children are compound heterozygotes and manifest the full Wolfram syndrome, in addition to cataracts.     

Thiamine-responsive megaloblastic anemia syndrome (TRMA) with cone-rod dystrophy

Thiamine-responsive megaloblastic anemia (TRMA) is an autosomal recessive disease in which the active thiamine uptake into cells is disturbed. The molecular basis underlying the disorder has been related to mutations in the gene SLC19A2 on chromosome 1q23.3 that encodes a functional thiamine transporter. The protein is predicted to have 12 transmembrane domains. TRMA is characterized by sensorineural deafness, diabetes mellitus, megaloblastic anemia, and cardiomyopathy. Optic nerve atrophy and retinal dystrophy have been reported in a small number of patients. We report a 15-year-old girl with TRMA and cone-rod dystrophy and confirm that retinal dystrophy may form part of the syndrome. Differential diagnosis of syndromes with deafness, diabetes mellitus, and optic nerve atrophy or retinal dystrophy are discussed. The authors suggest that ERG be performed in all patients with TRMA.     

Bilateral optic disc pit with maculopathy in a patient with cleft lip and cleft palate

Optic disc pit (ODP) is small, gray-white, oval depression found at the optic nerve head. It is a congenital defect that occurs due to imperfect closure of superior edge of the embryonic fissure. Cleft lip and palate are also congenital midline abnormalities occurring due to defect in the fusion of frontonasal prominence, maxillary prominence and mandibular prominence. There is only one case report describing the occurrence of ODP in a young patient with cleft lip and palate who also had basal encephalocele. We describe a 52-year-old patient with congenital cleft lip and palate with bilateral ODP with maculopathy but without any other midline abnormality.     

Diabetic maculopathy in a Jamaican population

Maculopathy is the commonest cause of severe visual loss from diabetic retinopathy in Jamaica [5]. Ophthalmic assessment of 158 black Jamaican maturity onset diabetics referred randomly from the primary and secondary health centres, demonstrated maculopathy in 48% of patients. Duration of diabetes was a strong risk factor for maculopathy (p<0.001). Poor compliance with diabetic and hypertensive therapy may influence the prevalence of maculopathy.     

Optical coherence tomography in a patient with chloroquine-induced maculopathy

We herein report the optical coherence tomography (OCT) findings in a case of chloroquine-induced macular toxicity, which to our knowledge, has so far not been reported. A 53-year-old lady on chloroquine for treatment of rheumatoid arthritis developed decrease in vision 36 months after initiation of the treatment. Clinical examination revealed evidence of retinal pigment epithelial (RPE) disturbances. Humphrey field analyzer (HFA), fundus fluorescein angiography (FFA) and OCT for retinal thickness and volume measurements at the parafoveal region were done. The HFA revealed bilateral superior paracentral scotomas, FFA demonstrated RPE loss and OCT revealed anatomical evidence of loss of ganglion cell layers, causing marked thinning of the macula and parafoveal region. Parafoveal retinal thickness and volume measurements may be early evidence of chloroquine toxicity, and OCT measurements as a part of chloroquine toxicity screening may be useful in early detection of chloroquine maculopathy.     

Clinical applications of multifocal electroretinography

The multifocal ERG using the m-sequence stimulation technique allows the derivation of 61 – 241 local ERG signals in a central visual field of about 60 degree diameter in a short time between 4 and 16 min. A recording in a light adapted state offers local information comparable to cone responses in the full-field ERG. Retinal functional losses due to regional disorders in outer retinal layers can be described in detail with this technique. In maculopathies decreased or absent central ERGs are found surrounded by normal ERG. The extent of the central lesion can be estimated. In diseases of the outer retina the pattern of distribution of multifocal ERG activity is similar to the the pattern of the visual field defect. In addition to decreased ERG amplitudes a delay of implicit time may be an important sign of pathology, i.e. the pronounced delay of implicit times in the periphery in retinitis pigmentosa and the implicit time delays in regions associated with retinal edema like CRVO and cystoid macula edema in intermediate uveitis. No simple correlation of the first order kernel multifocal ERG and field defects could be found in disorders of the ganglion cell layer. The multifocal ERG is therefore useful in the differential diagnosis of retinal and optic nerve diseases. This revised version was published online in July 2006 with corrections to the Cover Date.     

Pigmentary dispersion syndrome subsequent IOL implantation in P.C.

Excessive iris trauma during cataract surgery with or without IOL implantation and intermittent contact between the lens implant and the iris in the post-operative period may give rise to a pigment dispersion syndrome that can, in some cases, lead to a pigmentary glaucoma. This communication examines possible causes of the syndrome and the precautions to be undertaken in order to reduce its incidence.     

Optic pit maculopathy after laser-assisted in situ keratomileusis

CASE REPORT: Optic disc pit is an embryological malformation of the optic nerve that occurs in less than one in 10,000 people. It is 10%-15% bilateral, and 25% to 70% of patients develop a neurosensory macular detachment within the 2nd to 4th decade. COMMENTS: We report a case of unilateral optic disc pit maculopathy 2 months after laser-assisted in situ keratomileusis (LASIK) revision.     

Chorioretinal degenerative changes in the tilted disc syndrome

Ninety patients (163 eyes) with tilted disc syndrome were examined in order to show possible chorioretinal degenerative lesions associated with the typical ectasia of the infero-nasal fundus observed in this anomaly. Eighteen out of the 163 eyes had pigmentary accumulations, either branched, linear or dotted and five had roundish areas of chorioretinal atrophy. Furthermore, in 7 eyes areas of pigmentary atrophy at the posterior pole were observed. The most serious lesions were represented by macular choroidal neovascular membranes, seen in 3 eyes, which were responsible for the loss of vision in these eyes. A relationship was found between the depth of the ectasia, the degree of tilt of the optic disc and the development of chorioretinal degeneration. Because of possible complication by macular choroidal neovascularization, the tilted disc syndrome can not be regarded in every case as a benign and not evolutive ocular anomaly.     

Optic disc pit maculopathy: a review of diagnosis and treatment

Optic disc pit is a rare congenital defect which appears as a circumscribed greyish depression in the lamina cribrosa. Serous macular detachment is one of the most visually debilitating complications of optic disc pit, affecting 25–75 per cent of patients. Although there is a wide variety of treatment modalities available with varying degrees of success, there is yet no consensus in the optimal management of optic disc pit-associated maculopathy. This review discusses the literature on the pathogenesis, clinical presentation, diagnosis and treatment options.     

先天性视盘小凹并发黄斑病变的形态学特征

目的研究先天性视盘小凹并发黄斑病变的形态学特征及其在病程发展和激光治疗后的变化情况。设计回顾性病例系列。研究对象12例先天性视盘小凹合并黄斑病变患者。方法对临床诊断为先天性视盘小凹的患者资料进行回顾性分析,依据彩色眼底照相、相干光断层扫描及荧光素眼底血管造影检查结果结合既往有关小凹发病机制的理论进行分析归纳。对其中4例进行沿小凹区域的视盘边缘光凝治疗,观察期6—30个月。主要指标视力及黄斑病变特征。结果12例患者均合并浆液性黄斑病变,其中2例为单纯神经上皮脱离,2例为单纯神经上皮层间劈裂,其余两者兼有。病变区与小凹之间存在明确关联关系,病变程度与病程及视力也相关。2例合并先天性脉络膜缺损。3例激光治疗有效。结论视网膜神经上皮层间劈裂和神经上皮脱离是先天性视盘小凹合并黄斑病变的重要形态学改变,正确认识其与病程发展的关系有助于加深对发病机制的认识。激光治疗对部分患者有效。（眼科,2009,18：233—236）     

Wolfram syndrome 1 (WFS1) protein expression in retinal ganglion cells and optic nerve glia of the cynomolgus monkey

Wolfram syndrome (WFS1, OMIM 222300) is a rare genetic disorder associated with multiple organ abnormalities, most prominently optic nerve atrophy and diabetes. Mutations in the WFS1 gene coding for wolframin have been identified. The pathogenesis for optic nerve atrophy remains elusive. We here tested the hypothesis that wolframin is expressed in glial cells of the optic nerve and in retinal ganglion cells in the cynomolgus monkey. Paraffin sections through the retina and optic nerve were examined with immunohistochemistry using affinity-purified antibodies to wolframin. Retinal ganglion cells and optic nerve glial cells were found to be strongly labeled. Dual dysfunction of wolframin in optic nerve glial cells and retinal ganglion cells may explain the progressive optic nerve atrophy in Wolfram syndrome.     

黄斑病变患者多焦视网膜电图的变化

目的:观察黄斑病变多焦视网膜电图穴mERG雪特点,探讨mERG在黄斑功能测定中的有效性。方法:应用德国罗兰视觉诱发反应成像系统,对黄斑病变71 眼与正常人48眼进行mERG测定,记录103个视网膜部位的一阶反应(first orderkernel,FOK)比较分析视网膜后极部不同区域a波和b波的平均反应密度值和潜伏期,并观察其三维图的改变。结果:黄斑病变患者1～3环a、b波平均反应密度下降,与正常值比较有显著差异。5、6环平均反应密度下降,无显著差异。1～6环a、b波平均潜伏期较正常组明显延长,三维图形上主要特征为中心凹及黄斑振幅明显降低,严重者反应呈平坦。结论:mERG能客观地对黄斑病变局部视网膜功能进行定量定位测定,是评价黄斑病变的一种有效客观检测手段,为疾病诊断和治疗效果客观的测定提供了一种有效方法。     

Comparative findings in childhood‐onset versus adult‐onset optic disc pit maculopathy

Purpose: To compare the clinical characteristics of eyes with childhood‐onset to those with adult‐onset optic disc pit maculopathy. Methods: Twenty‐seven eyes of 25 patients with optic disc pit maculopathy were reviewed. The clinical characteristics, clinical history including a history of blunt trauma, ophthalmoscopic evaluations and intraoperative findings in the childhood‐onset (age <15 years, four eyes of four patients) cases were compared with those in the adult‐onset (≥15 years, 23 eyes of 21 patients) cases of optic disc pit maculopathy. The strength of the vitreous adhesions was graded by what was required to create a posterior vitreous detachment (PVD); grade 1 = with vitreous cutter, grade 2 = by microhook or forceps and grade 3 = by forceps with removal of remnants of Cloquet’s canal. Results: The incidence of visual impairments following blunt trauma was significantly higher in childhood‐onset (three of four eyes) than that of adult‐onset (0 of 23 eyes, p = 0.0014). Vitreous surgery with creation of a PVD was performed in the four childhood‐onset eyes and 18 adult‐onset eyes after an absence of a spontaneous resolution. The grade of the vitreous adhesions was significantly higher in childhood‐onset than in adult‐onset eyes (p = 0.0096). Conclusions: An ocular trauma may provide an opportunity to detect optic disc pits. However, childhood‐onset optic disc pit maculopathy was noted most commonly following blunt ocular trauma in eyes with a strong vitreous adhesion to the optic disc margin.