C. T. Langerhorst

Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2.

Charcot‐Marie‐Tooth (CMT) neuropathy with visual impairment due to optic atrophy has been designated as hereditary motor and sensory neuropathy type VI (HMSN VI). Reports of affected families have indicated autosomal dominant and recessive forms, but the genetic cause of this disease has remained elusive.

Histopathologic Effects of Mitomycin C After Trabeculectomy in Human Glaucomatous Eyes With Persistent Hypotony

We evaluated the histopathologic findings in seven patients who underwent surgical revision of the filtration site after trabeculectomy with mitomycin C because of persistent hypotonous maculopathy. Light microscopic examination of subconjunctival tissue and sclera demonstrated hypocellularity of fibroblasts and disruption of the normal architecture. Tissue fragments at the margin of the bleb wall demonstrated scarring and contained multiple fibroblasts. Additionally, we investigated the histopathologic changes in an eye obtained from a patient who died one week after a trabeculectomy with mitomycin C. Transmission electron microscopy showed myelin figures, increased melanolipofuscin granules, vacuolated cytoplasm, and disrupted mitochondria of the ciliary body epithelium underlying the site of mitomycin C application. On the basis of these findings, both overfiltration because of tissue disorganization of the filtering bleb and aqueous hyposecretion because of ciliary body toxicity might be involved in the causes of persistent hypotony after mitomycin C trabeculectomy.

Retinal Nerve Fiber Layer Assessment by Scanning Laser Polarimetry and Standardized Photography

PURPOSE To determine whether, in a clinical setting, scanning laser polarimetry and retinal nerve fiber layer photography provide equivalent information on the retinal nerve fiber layer. METHODS We prospectively studied 60 patients with glaucoma or ocular hypertension and 24 healthy subjects. With scanning laser polarimetry, an estimate of the cross section of the retinal nerve fiber layer was obtained. By using a photographic reference set, we quantified photographs of the retinal nerve fiber layer. Visual fields were used to relate the results of both methods to functional damage. RESULTS The scanning laser polarimetry measurements yielded reproducible cross-section values (coefficient of variation, 6.6%). Comparison of cross-section values and photograph scores gave Pearson correlation coefficients smaller than r = .4 (P < .01), improving to a maximum of r = .53 after compensation for offset. When cross-section values were compared to the mean deviation of the visual field, the Spearman correlation coefficients varied from an r of -.34 to -.53 (P < .01). Correction for offset resulted in an r of -.54 to -.65. When photograph scores and mean deviation of the visual field were compared, the Spearman correlation coefficients varied from an r of -.65 to -.71 (P < .01). CONCLUSIONS Because r was maximal at .53, the information on the retinal nerve fiber layer obtained with scanning laser polarimetry and photography seems not equivalent. This result could not have been because of lack of reproducibility. Although the results suggested possible offset in scanning laser polarimetry, other methodologic differences must be considered to explain the differences between the two techniques.

Treatment of Hypotonous Maculopathy After Trabeculectomy With Mitomycin C

We treated 34 eyes of 32 patients who developed a hypotonous maculopathy after a trabeculectomy with mitomycin C with various treatment strategies. Placement of a Megasoft Bandage Contact Lens in 24 eyes did not result in a notable increase in intraocular pressure or visual acuity. Intrableb injection of autologous blood in 22 eyes resulted in a mean +/- standard deviation (S.D.) increase in intraocular pressure from 4.3 +/- 1.8 mm Hg before injection to 8.6 +/- 4.6 mm Hg after injection. Mean logMAR visual acuity improved from 0.71 +/- 0.40 to 0.32 +/- 0.25. After a surgical revision of 16 eyes, intraocular pressure increased from 4.1 +/- 1.9 mm Hg to 11.3 +/- 4.0 mm Hg, and logMAR visual acuity improved from 0.61 +/- 0.30 to 0.22 +/- 0.24. At the last follow-up examination (12.2 +/- 5.1 months after the trabeculectomy), 31 eyes (91.2%) had an intraocular pressure greater than 6 mm Hg. Hypotonous maculopathy after trabeculectomy with mitomycin C can be treated successfully by autologous blood injection and surgical revision of the filtration site.

Blue-yellow perimetry in the detection of early glaucomatous damage

A perimetric method using blue stimuli on a yellow background was compared with perimetry using white stimulion on a white background as a method of detecting glaucomatous damage. Meridian perimetry was used with an adapted Tübinger perimeter. The difference between the blue-on-yellow meridian and the white-on-white meridian was subdivided into two parts: the general blue sensitivity loss (GBSL), probably due to optical factors, and the corrected blue sensitivity loss (CBSL), probably due to glaucoma. Nine normals, fourteen primary open angle glaucoma (POAG) patients and nine ocular hypertensives (OHT) were tested. All POAG patients and some of the OHT group showed higher CBSL values than the controls. The blue-yellow meridian showed broader and deeper defects than the white-white meridian in all of the POAG group; some of the OHT group had defects in the blue-yellow meridian that were not present in the white-white meridian.In conclusion, blue on yellow perimetry shows promise as a method for more sensitive detection of early glaucomatous damage.

Grading of Retinal Nerve Fiber Layer With a Photographic Reference Set

PURPOSE We developed a new quantitative approach for the evaluation of diffuse atrophy of the retinal nerve fiber layer. METHODS A simultaneous, visually supported grading system was designed, which consisted of a set of 25 reference photographs, numbered from 25 (broad, clearly striated nerve fiber bundles) to 1 (no nerve fibers visible). We prospectively evaluated this method by matching 60 retinal nerve fiber layer photographs of patients with glaucoma or ocular hypertension and normal subjects to the reference photographs twice by three observers with varying experience levels in evaluating retinal nerve fiber layer RESULTS Intraobserver and interobserver reliability, evaluated by the intraclass correlation coefficient statistics, was excellent (intraclass correlation coefficient > 0.8). Intraclass correlation coefficients within observers were from 0.89 to 0.98 (lower limits 905% confidence interval, 0.84 to 0.97), and intraclass correlation coefficients between observers were from 0.81 to 0.91 (lower limits 95% confidence interval, 0.50 to 0.87). Clinical validity, in which the scores for upper and lower halves of photographs were compared with the mean deviation of the Humphrey 30-2 visual field program by using the Spearman correlation coefficient, was substantial (r = -.68, P < .01 for upper photo score and lower field mean deviation, r = -.53, P < .01 for lower photo score and upper field mean deviation). CONCLUSIONS By using a reference set of of photographs of the retinal nerve fiber layer, we defined a method to derive a quantitative measurement of retinal nerve fiber layer with good reliability and to extend evaluation of retinal nerve fiber layer photographs to nonspecialists.

Is there general reduction of sensitivity in glaucoma

Ten normal controls, ten ocular hypertensive patients, ten high tension, 12 medium tension and nine low tension glaucoma patients were studied prospectively by means of automated static perimetry. Multiple double threshold measurements were obtained during at most three years. A computer algorithm estimated for each visual field the Individual General Sensitivity IGS, in which local defects do not contribute. Thus we were able to estimate pure general reduction of sensitivity by comparing the IGS to age-corrected normal reference values. No significant difference in mean general reduction of sensitivity was found between the glaucoma patients and the normal group. Patients with local defects in one field half only also showed IGS values not different from normals. Our findings indicate that the impression of ‘general’ sensitivity loss may be caused by the presence of multiple local defects, and is not a phenomenon in itself.

EXTENSION OF THE CLINICAL SPECTRUM OF DANON DISEASE

Danon disease is caused by mutations in the lysosome-associated membrane protein 2 (LAMP2).1 It is an X-linked dominant disorder characterized by severe cardiomyopathy, mental retardation, and mild myopathy in men, and cardiomyopathy in female carriers.2 All mutations reported so far have resulted in absence of LAMP2 staining in affected men.1–4 ### Case reports. The proband, III-4 (figure e-1 on the Neurology ® Web site at www.neurology.org), with normal intelligence, was referred at age 46. Since childhood, he had slowly progressive weakness of legs and later arms, with subsequent dysarthria and swallowing difficulties. He is now 63 and is almost completely wheelchair bound. His vision has gradually diminished to finger counting. Examination showed a myopathic face, gynecomastia, moderate weakness of limb girdle muscles, and minor distal weakness. Perimetry demonstrated central scotomas, while fluorescein angiography showed a Bullseye maculopathy, but electroretinography was normal. At the age of 61 a pacemaker was implanted because of a sick sinus syndrome. Echocardiography revealed left ventricular hypertrophy with preserved systolic function. Subject III-3 presented at the age of 63 years with muscle weakness since age 45. His intellect and vision were normal. In retrospect, he had been a little weaker than his peers since his teens. He showed predominant …

Usefulness of the Henson Central Field Screener for the detection of visual field defects, especially in glaucoma

The Henson Central Field Screener is a recently marketed, relatively inexpensive campimeter with semi-automated registration of responses. The strategy used is suprathreshold, eccentricity-compensated, multiple stimulus static perimetry. The clinical usefulness of this apparatus was tested in a number of glaucoma patients, glaucoma suspects and normals, as well as in subjects with other ocular disorders, for whom stable visual fields as tested with other perimeters were available. The results obtained with the Henson Screener are generally in agreement with the known defects. The apparatus has some drawbacks, however.

Two amino-acid substitutions in the myelin protein zero gene of a case of Charcot–Marie–Tooth disease associated with light-near dissociation

Charcot-Marie-Tooth disease caused by mutations of the myelin protein zero gene demonstrates considerable phenotypical variability. We describe a 45-year-old female with a peripheral neuropathy with demyelinating and axonal features, pes cavus and pupillary light-near dissociation. She was heterozygous for two mutations in the myelin protein zero gene (His81Tyr and Val113Phe), both present on the same allele. Our patient shows a less severe phenotype than previously described patients with a His81Arg mutation. Multiple mutations in the myelin protein zero gene, as well as Charcot-Marie-Tooth with pupillary abnormalities have previously been described in rare instances. However, concurrent occurrence of both phenomena is a novel finding.