Saccadic eye movements are impaired in Duchenne Muscular Dystrophy

Extraocular muscles are generally considered to be spared in Duchenne Muscular Dystrophy (DMD). However, this assumption is based mainly on clinical observations, as systematic eye movement recordings have been performed in a very limited number of cases. Our goal was to analyze several saccade parameters in a higher number of cases, in order to reveal a possible ocular-motor impairment in DMD. Data were collected from a population of 9 subjects with DMD and 9 healthy male subjects of comparable age as controls. We used the electrooculographic (EOG) technique coupled with advanced digital signal processing; saccade duration, amplitude, mean velocity, peak velocity and K factor (ratio mean/peak velocity) were measured. The DMD group showed saccades with significantly longer duration and lower velocity, with respect to controls; these differences were accounted for mainly by the largest movements, whereas there were no significant differences at the smallest eccentricity tested (3 deg). Neither amplitude nor K factor were significantly different from controls for any of the eccentricities tested. To our knowledge, this is the first study to suggest significant impairment of eye movements in Duchenne muscular dystrophy.     

Correlations Between Dark-Adapted Rod Threshold Elevations and ERG Response Deficits in Duchenne Muscular Dystrophy

PurposeThe purpose of this study was to characterize changes in the full-field flash electroretinogram (ERG) in association with psychophysical dark-adapted visual thresholds in patients with genetically characterized Duchenne muscular dystrophy (DMD) either lacking Dp427 (Up 30) or at least Dp260 in addition to Dp427 (Down 30).MethodsTwenty-one patients with DMD and 27 age-similar controls participated in this study. Dark-adapted (0.01, 3.0, and 10 cd.s/m² flashes) and light-adapted (3.0 cd.s/m² flash) ERGs were recorded following International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocols. Visual detection thresholds to 625-nm (cone function) and 527-nm (rod function) light-emitting diode (LED) flashes (2 degree diameter) were measured during a dark adaptation period after a 1-minute exposure to a bleaching light (3000 cd/m²). Initially, 8 minutes of interleaved 625-nm and 527-nm thresholds were measured. After an additional 5 minutes of dark-adaptation, a second set of threshold measurements to 527-nm stimuli was performed during the subsequent 6 minutes.ResultsDark-adapted b-wave amplitude was significantly reduced to all strengths of flash and a-wave in response to the strong flash stimulus was delayed (15.6 vs. 14.7 ms, P < 0.05) in patients with Down 30 compared with controls. Dark-adapted cone thresholds did not differ among the groups (−2.0, −1.8, and −1.7 log cd/m² for Down 30, Up 30, and controls, respectively, P = 0.21). In contrast, dark-adapted rod thresholds were elevated (F_(2,36) = 8.537, P = 0.001) in patients with Down 30 (mean = −3.2 ± 1.1 log cd/m²) relative to controls (mean = −4.2 ± 0.3 log cd/m²). Dark-adapted b-wave amplitudes were correlated with dark-adapted rod sensitivity in patients with DMD (Spearman Rho = 0.943, P = 0.005). The changes were much smaller or absent in patients with intact Dp260.ConclusionsDp260 is particularly required for normal rod-system function in dark adaptation.     

Electroretinal changes in the presence of a carbonic anhydrase inhibitor

A specific carbonic anhydrase activity inhibitor (methazolamide) was injected into one vitreous body each of 4 New Zealand White rabbits. Electroretinograms (ERG) were recorded before and several times after the methazolamide injection. The stimulus levels maximized the rod and cone response characteristics of the rabbit ERG. The effects of methazolamide were followed over 5 h. During this time, the electroretinograms showed a decline in amplitude of both a and b waves at both stimulus levels. The data support the involvement of carbonic anhydrase in the excitatory physiological events in the retina. Preliminary evidence indicates a slow recovery of the carbonic-anhydrase-inhibited ERG.     

Alterations of the retino-cortical conduction in patients affected by Classical Congenital Muscular Dystrophy (Cl-CMD) with merosin deficiency

Immunocytochemical analysis of the laminin alpha-2 (merosin) chain in the muscle of patients with Classic Congenital Muscular Dystrophy (Cl-CMD) differentiates the types of the disease associated with a merosin deficit from those that are merosin positive. Patients with Central Nervous System involvement in merosin negative Cl-CMD always present alterations of the white matter at RMI, but usually these are not clinically significant. While ocular malformations (microphthalmia, alterations of the anterior chamber, of the retina, or of the angle and cataract) and damage to the Central Nervous System are described in some subtypes of CMD (Muscle Eye Brain disease, Walker Warburg Syndrome), ocular involvement and retino-cortical conduction in merosin negative Cl-CMD are not well known. This study reports on four patients affected by merosin negative Cl-CMD. All these patients presented important alterations of the white matter associated with ventricular enlargement and, in one case, with pachygyria and micropolygyria. Refraction, visual acuity, ocular motility, anterior segment and fundus were examined. ERG Maximal, Cone and Rod response, VEP transient pattern reversal was carried out as well. Significant alterations at the standard ophthalmologic examination or of the electroretinogram responses were not registered while, in all cases, important modifications in retino cortical conduction (reduction in amplitude, increase in latency, reduction in amplitude on the lateral derivations) were observed, demonstrating involvement of the optic pathway at different levels during the course of this disease. This revised version was published online in July 2006 with corrections to the Cover Date.     

双眼颗粒状角膜营养不良合并Fuchs角膜内皮营养不良一例

患者，女，69岁，中国汉族人。因“双眼干涩伴视物模糊1个月”于2016年7月21日就诊于温州医科大学附属第二医院眼科。既往否认糖尿病、高血压、风湿病等病史，否认家族遗传病史和药物过敏史。入院常规检查未见明显异常。眼科常规检查：最佳矫正视力（BCVA）右眼0.30，左眼0.25；非接触眼压计测量（Noncontact tonometer，NCT）：右眼14.5 mmHg（1 mmHg= 0.133 kPa），左眼15.6 mmHg；双眼结膜无充血，双眼角膜中央可见浅基质层多发的圆形面包屑样混浊（见图1A、1D）；裂隙灯显微镜下后弹力层可见散在局限性增厚，滴状赘疣物可见（见图1B、1E），未见角膜水肿；前房深，晶状体轻度皮质性混浊，双眼眼底视盘边界清，C/D=0.3，黄斑反光存在。角膜内皮镜检查：右眼中央角膜内皮细胞数2 550 个/mm2，变异系数为32%，厚度为565 μm，左眼中央角膜内皮细胞数2 457 个/mm2，变异系数为38%，厚度为558 μm，双眼部分角膜内皮细胞增大呈多形性改变，可见病理性暗区（见图1C、1F）。诊断：双眼颗粒状角膜营养不良，双眼Fuchs角膜内皮营养不良，双眼老年性白内障。考虑到该病为染色体异常疾病，建议患者进行基因测序明确突变基因，患者因经济原因，拒绝检查。考虑到目前尚无有效治疗方法，且患者自觉目前视力状况下生活无障碍，拒绝进一步治疗。向患者说明情况，建议门诊随访观察，予以角膜营养滋润药物和抗白内障药物，门诊定期随访，必要时行角膜移植手术联合或不联合白内障摘除+人工晶状体植入术。     

Prevalence of Granular Corneal Dystrophy Type 2 (Avellino Corneal Dystrophy) in the Korean Population

Purpose: This study investigates the prevalence of granular corneal dystrophy type 2 (GCD2; Avellino corneal dystrophy) in the Korean population.

Methods: GCD2 homozygotes were identified through a collaboration of Korean referral centers for corneal disease. The genetic status of the patients and their immediate families were verified by DNA analysis. A lower bound for the gene prevalence was calculated using a model based on the Hardy-Weinberg principle. A second population-based model was developed to correct for known underestimation in the primary model. The corrected model used population data from the 2005 Korean census and fertility rates from historical Korean census data.

Results: We identified 21 individuals homozygous for GCD2 (R124H mutation) from 16 Korean families. From this, we estimate that the overall prevalence (combining heterozygotes and homozygotes) is at least 8.25 affected persons/10,000 persons. Our corrected estimate for overall prevalence is 11.5 affected persons/10,000 persons.

Conclusion: We present the first estimate of the prevalence of GCD2. Although uncommon, the prevalence of GCD2 in Korea is greater than anticipated. We believe that our approach could potentially be applied to estimating the prevalence of other rare diseases.     

Muscular activity and perimetric thresholds

Static and kinetic peripheral luminance thresholds were measured by means of a Goldmann perimeter along oblique meridians in monocular vision. In a main group of 33 young and healthy subjects these measurements and visual reaction time assessments were made successively at rest, when cycling without load, when cycling with load using aerobic energy supply, when cycling with load using anaerobic energy supply and twice again at rest. Another group of subjects did not pedal and served as controls. The results show that peripheral visual sensitivity increases faintly but significantly during muscular exercise. When assessed by static perimetry the sensitivity increase is grossly proportional with load and is thus greatest in anaerobic condition, while kinetic sensitivity differs by a sensitivity decrease when passing from aerobic to anaerobic exercise. The reported modifications in perimetric sensitivity during dynamic muscular exercise seem related to changes in alertness.     

Prevalence of Generalized Retinal Dystrophy in Denmark

Purpose: Generalized retinal dystrophy is a frequent cause of visual impairment and blindness in younger individuals and a subject of new clinical intervention trials. Nonetheless, there are few nation-wide population-based epidemiological data of generalized retinal dystrophy. The purpose of this study was to examine the prevalence and diagnostic spectrum of generalized retinal dystrophy in the Danish population.

Methods: A population-based cross-sectional study with data from the Danish Retinitis Pigmentosa Registry that comprises all patients in Denmark with generalized retinal and chorioretinal dystrophies from the 19th century to the present. Among 3076 registered cases, the primary diagnosis of generalized retinal dystrophy was assessed by chart review, including fundus photographs and electroretinograms. Demographic data on the Danish population were retrieved from Statistics Denmark.

Results: Of the 5,602,628 Danish citizens on January 1, 2013, 1622 patients were registered as having a generalized retinal dystrophy and were alive and living in Denmark, corresponding to a prevalence of 1:3,454. In 28% of cases the eye condition was part of a syndrome, while the remaining 72% had eye disease only. Aside from simplex cases (45%), the most common hereditary pattern was autosomal recessive (23%).

Conclusion: This epidemiological survey demonstrates that the prevalence of generalized retinal dystrophy in the Danish population is 1:3454. Many of the dystrophies are the subjects of clinical intervention trials, and nation-wide epidemiological data can help assess the burden of the disease and the future need for treatment.