Rhodopsin C110Y mutation causes a type 2 autosomal dominant retinitis pigmentosa.

PURPOSE: The RHO C110Y mutation has been recently reported to cause a phenotypically unspecified form of autosomal dominant retinitis pigmentosa (adRP). The study of a family affected with this mutation allowed us to hereby describe the genotype/phenotype correlation associated with the RHO C110Y mutation. METHODS: A six-generation pedigree cosegregating adRP and RHO C110Y in ten accessible individuals was ophthalmologically investigated. All family members affected with RP went through complete eye examination and ERG testing. RESULTS: The disease first manifested with nyctalopia during adulthood and slowly progressed over the next decades towards tubular visual field defects and relatively preserved central vision. Ophthalmoscopically, the fundus remained almost unaltered until the end of the third decade of life, and then slowly progressed towards typical RP changes with minimal macular involvement by the eighth decade. Color vision remained unaltered. Earliest ERG alteration was limited to the rod system followed by a rod-cone pattern. Scotopic and photopic ERG were recordable until the fourth and sixth decades, respectively. DISCUSSION: RHO C110Y-associated adRP is characterized by a late onset and a mild progression compatible with type 2 or regional RP with little intrafamilial phenotypic variability and complete penetrance. Characterization of genotype-phenotype correlations plays a role in the improvement of genetic and prognostic counselling.

Full characterization of the maculopathy associated with an Arg-172-Trp mutation in the RDS/peripherin gene.

The objective of this study was to fully characterize the macular dystrophy phenotype and genotype in a large family of the Zermatt area of Switzerland. Clinical and molecular studies of the family included a comprehensive eye examination and a mutational analysis of the RDS, rhodopsin, and TIMP-3 genes. In selected cases, fluorescein angiography, perimetry, and electroretinography were performed. Forty-two family members at risk of expressing the maculopathy were studied. Of these, 24 were found to be clinically affected. The severity of macular disease in these patients was clearly age-related and different stages of progression were identified. Central pigmentary alterations were seen in adolescent patients, while patients in their late teens and twenties exhibited drusen-like deposits. Later, these defects formed focal areas of atrophy which eventually led to central geographic atrophy with severe visual loss by the fifth decade and cone-rod dysfunction. The transmission of this condition is autosomal dominant with complete penetrance. The underlying genetic defect is a mutation in codon 172 of the RDS/peripherin gene, a gene expressed in both rods and cones, which results in the substitution of tryptophan for an arginine residue at that position. 'Zermatt macular dystrophy' is a dominant, age-related, progressive macular dystrophy which in later stages resembles atrophic age-related macular degeneration. The size of the family studied allowed definition of the clinical spectrum of this condition and identification of the related genetic defect which allows more precise diagnosis and counseling.

[Toxic retinopathy caused by intravitreal injection of amikacin and vancomycin]. / Rétinopathie toxique sur injection intravitréenne d'Amikacine et Vancomycine.

CASE REPORT: Referred because of a right corneal perforation with cellular reaction in anterior chamber, a patient was sutured and treated with a single intravitreal injection of 0.2 ml (1 mg) Amikacin and 0.2 ml (1 mg) Vancomycin. Whereas the retina was normal before the injection, a diffuse retinal edema with intra- and preretinal hemorrhages was noted 12 hours postoperatively. Visual acuity was markedly reduced. ERG and visual field was also abnormal. CONCLUSION: This case demonstrates that a single intravitreal injection of Amikacin and Vancomycin at usual concentration may induce retinal toxicity with permanent damage.

[Loss of ganglion cells in the retina secondary to vincristine therapy]. / Perte des cellules ganglionnaires de la rétine secondaire à la prise de vincristine.

We report the case of a 25-year-old black female from Zaire with AIDS diagnosed 2 years earlier. Nine months before her death, she was treated for a disseminated Kaposi sarcoma with vincristin, adryamycin and bleomycin. At that time, visual acuity was normal and ophthalmologic examination was unremarkable except for the presence of bilateral Drusen and a cotton wool spot OS. Three months after the onset of chemotherapy, the patient complained of progressive visual field constriction, which progressed to blindness within a 4 month period. Five months after the onset of the tri-therapy a bilateral CMV retinitis developed, which was successfully treated by intravitreous injections of ganciclovir. This therapy was stopped as soon as blindness was established, with subsequent massive bilateral recurrence of the CMV retinitis. Histologic examination showed complete atrophy of the retinal ganglion cells and areas of CMV retinitis. The optic nerve was demyelinated and exhibited astrocytic gliosis. Immunohistochemistry confirmed the presence of CMV in infected retina and revealed the absence in the optic nerve of the class III beta-tubulin isotype and of the 200 kd neurofilament subunit. In contrast, oculomotor nerves appeared intact. The presence of HIV in the eye and in the optic nerve was excluded using PCR technique. The retinal ganglion cell loss and optic nerve atrophy appeared to be purely degenerative in nature, since there was no evidence of vascular occlusion, inflammation or retrobulbar compressive process. We therefore conclude that blindness was caused by vincristine therapy. The patient actually received 22 mg of vincristin intravenously in 11 courses over 7 months, although discontinuation was recommended by us after 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Irregularities in the flicker sensitivity curve.

The flicker sensitivity of the human eye may be characterized by the De Lange curve (temporal modulation transfer function plot). In the curves of two out of eight observers, D. H. Kelly [J. Opt. Soc. Am. 52,940-947 (1962)] found three peaks instead of one, as had been reported in previous publications, and suggested that they are related to the three mechanisms of color vision. Several investigations have been based on this suggestion, but there has been no confirmation of his observation. In this paper, a new measuring method was devised and the existence of the peaks was confirmed, but the hypothesis that they are related to color processes was questioned.

Artificially increasing intraocular pressure causes flicker sensitivity losses.

It has been reported that psychophysical flicker sensitivity, electroretinogram (ERG), pattern electroretinogram (P-ERG), and visual evoked cortical potential (VECP) responses are affected by ocular hypertension and glaucoma. Moreover, it has also been revealed that artificially augmented intraocular pressure (IOP) impairs electrophysiologic responses. In this investigation the authors varied the levels of IOP of ten normal subjects and determined their flicker sensitivities at these levels. Temporarily elevated IOPs were produced by exerting pressure on the eyeball through the eyelids by a new type of ophthalmodynamometer. The results obtained showed that increasing IOP produced loss of flicker sensitivity. For an IOP of 27.2 +/- 2.1 mm Hg, significant losses occurred in the range of frequencies lower than 20 Hz. For a higher IOP (40.7 +/- 2.1 mm Hg) the loss was significantly at frequencies higher than 5 Hz. However, the critical flicker frequency was not affected significantly at either level of IOP. The authors also discovered a phenomenon, called "curtain phenomenon," in that for a critical level of IOP, a high flicker frequency stimulus could completely fade out. The authors' results suggest that the psychophysical flicker sensitivity measurement is a more sensitive technique for the investigation of the effect of the variation of the IOP and that the curtain phenomenon constitutes an interesting indication for additional study of the ocular hypertension mechanism.

[Electromechanical flash stimulator for erg-pev (author's transl)]. / Stimulateur à éclairs électromécaniques pour ERG-PEV.

In order to avoid electrical interference and the noice caused by a gas discharge tube (flash), the authors have developed a stimulator using mechanical flash as light modulator for ERG and PEV. Flash duration is 2 ms regardless of frequency. This apparatus is now on the market.

[Biomicroscopic pneumatic ophthalmodynamography (author's transl)]. / Obhtalmodynamographie pneumatique au biomicroscope.

One hundred volunteers were examined with a new pneumatic dynamometer which permits the use of the slit lamp and the Hruby lens, this is a noncorneal-contact instrument indicating the relationship between diastolic systemic pressure and diastolic ophthalmic pressure; in the latter case, the pressures in the two eyes are compared.

Visual stimulator.

An easily portable apparatus for flicker fusion experiments is described. It uses crossed polarizers to produce modulated beams and a light guide made of optical fibers to mix these beams for producing a sinusoidally modulated stimulus of which the frequency, the modulation amplitude, the luminance, the color adaptation light, and the field size can be varied independently.

[Comparison of macular electroretinography and psychophysical tests in diabetic retinopathy with intraretinal edema]. / Electrorétinogramme maculaire et tests psychophysiques comparés dans la rétinopathie diabétique avec oedème intrarétinien.

Short comparison between psychophysic and electrodiagnostic tests in 20 eyes with macular edema from diabetic retinopathy. De Lange's curve, the critical flicker frequency in central fixation and the macular ERG are compared with the classical EOG and global ERG data. The methodology is briefly described. It allows a new approach of the macula and the macular ERG responses confirms the clinical tests.

[Does the intraretinal contusive syndrome exist?]. / Le syndrome contusif intrarétinien existe-t-il?

An ocular trauma may be followed only by a decrease in visual acuity without any tissular alteration. The measurement of the flicker sensitivity permits to hypothesize that the origin of the disturbance is in the retina itself. We postulate, therefore, the existence of a trauma of the lateral inhibition and we propose the term contusive intraretinal syndrome.

[From perceptive flicker to macular ERG by sinusoidal stimulation (author's transl)]. / Vom perzeptiven Flicker zum makulären ERG durch sinusoidale Stimulation.

A short presentation is given of the instrument used for perceptive flicker and for macular ERG. A modified de Lange's curve is obtained (the trimodal curve) and a macular ERG response is obtained from stimulation within a theoretical angle of 46 minutes of are.

[Fluorescein angiography of anterior segment of the eye (author's transl)]. / Angiographie du segment antérieur

This method can supply an unreplaceable iconographic document in order to follow the course of illness. A certain distinction between tumoral and nontumoral lesions is not possible. But this method is useful in the treatment of vascularized leucoma because it shows us the exact locus where the laser must be applied before the corneal graft is made.

[Critical flicker frequency (CFF) in the central and peripheral visual field (author's transl)]. / Fréquence critique de fusion dans le champ visuel central et périphérique. Résultats préliminaires

Two methods with their instruments are presented. First the measurement of C.F.F. in modified Goldmann perimeter. Secondly the register of the trimodal curve. The term "flicker acuity" is proposed with its mathematical translation. The second method concerns an original papillophotometer which can perhaps explore the color vision mechanism.

Color angiography and angioscopy.

The authors present the results of their color fluorescein angiographies carried out with a pocket retinograph equipped with new interferential filters. After the graphic examination, they propose to use these same filters mounted on different instruments for binocular and monocular angioscopy. Their results show that retinal vessels are translucid and that their color changes according to their background. The authors termed this change 'versicolored effect'. Moreover, color angiography with these new filters eliminates pseudofluorescence and adds to the fluoroscopic examination an element of analytic perfection, thus giving a new opening to differential diagnosis in endo-ocular diseases.