X linked cone-rod dystrophy, CORDX3, is caused by a mutation in the CACNA1F gene.

BACKGROUND: X linked cone-rod dystrophy (CORDX) is a recessive retinal disease characterised by progressive dysfunction of photoreceptors. It is genetically heterogeneous, showing linkage to three X chromosomal loci. CORDX1 is caused by mutations in the RPGR gene (Xp21.1), CORDX2 is located on Xq27.2-28, and we recently localised CORDX3 to Xp11.4-q13.1. We aimed to identify the causative gene behind the CORDX3 phenotype. METHODS: All 48 exons of the CACNA1F gene were screened for mutations by DNA sequencing. RNA from cultured lymphoblasts and peripheral blood activated T lymphocytes was analysed by RT-PCR and sequencing. RESULTS: A novel CACNA1F mutation, IVS28-1 GCGTC>TGG, in the splice acceptor site of intron 28 was identified. Messenger RNA studies indicated that the identified mutation leads to altered splicing of the CACNA1F transcript. Aberrant splice variants are predicted to result in premature termination and deletions of the encoded protein, Ca(v)1.4 alpha1 subunit. CONCLUSION: CACNA1F mutations cause the retinal disorder, incomplete congenital stationary night blindness (CSNB2), although mutations have also been detected in patients with divergent diagnoses. Our results indicate that yet another phenotype, CORDX3, is caused by a mutation in CACNA1F. Clinically, CORDX3 shares some features with CSNB2 but is distinguishable from CSNB2 in that it is progressive, can begin in adulthood, has no nystagmus or hyperopic refraction, has only low grade astigmatism, and in dark adaptation lacks cone threshold and has small or no elevation of rod threshold. Considering all features, CORDX3 is more similar to other X chromosomal cone-rod dystrophies than to CSNB2.

A new genetic locus for X linked progressive cone-rod dystrophy.

X linked progressive cone-rod dystrophy (COD) is a retinal disease primarily affecting the cone photoreceptors. The disease is genetically heterogeneous and two loci, COD1 (Xp21.1-11.4) and COD2 (Xq27.2-28), have been previously identified. COD1 was recently shown to be caused by mutations in RPGR exon ORF15 (Xp21.1), the gene that is also responsible for RP3 type retinitis pigmentosa. In this study, we performed a linkage study to map the disease gene in a large Finnish family with X linked cone-rod dystrophy, using a panel of 39 X chromosomal markers. Several recombinations between the disease gene and markers in the Xp21.1-p11.4 region have excluded COD1 as a candidate locus in this family. Consistent with the linkage results, no mutation was detected by direct PCR sequencing of the coding region of RPGR, including exon ORF15. The COD2 locus has been also excluded as the site of the gene on the basis of negative lod score values obtained for COD2 linked markers. The disease causing gene of the studied COD family has been localised between the markers DXS10042 and DXS8060 on Xp11.4-q13.1. Positive pairwise lod scores >3 were obtained for markers DXS993, MAOB, DXS1055, and DXS1194. Since this locus is distinct from the previously identified two loci, COD1 and COD2, our results establish a new third genetic locus for X linked progressive cone-rod dystrophy and further expands our knowledge about the genetic heterogeneity underlying this disease entity.

No reversion in vigabatrin-associated visual field defects.

Sixty adult patients with partial epilepsy who have been treated with vigabatrin for 7 months to 14 years as mono- or add-on therapy were examined with repeated kinetic Goldmann perimetries to evaluate the prevalence, risk factors, and long-term outcome of vigabatrin-associated visual field defects. A follow-up examination was performed after 4 to 38 months (mean, 15 +/- 7) in 55 patients, 29 of whom had discontinued vigabatrin therapy. Neither reversion nor progression in visual field constriction was observed.

Normal test scores in the Farnsworth-Munsell 100 hue test.

One hundred and sixty persons aged from 10 to 69 years (106 women, 54 men) with healthy eyes were studied with the Farnsworth-Munsell 100 hue (FM100) test. The mean of the results in the total scores and in the individual box scores in the right and left eye were calculated. The total score was also separately calculated in women and men. The test was administered under the illumination of Macbeth Easel lamp, 1000 lux, and the right eye was tested first. The results were calculated in six different age groups, 10-19 years, 20-29 years, etc. The mean of the total scores in the right eye varied from 7.44+/-2.46 (SD) to 10.07+/-2.03 in different age groups and in the left eye from 7.56+/-2.36 to 10.16+/-2.68. The scores changed significantly with the age: the correlation between the age and the test scores by linear regression gave significant results, in the right eye (R = 0.308, P = 0.0001), and in the left eye (R = 0.246, P = 0.0021). The present study with the normal error scores in the FM100 test and its individual boxes in persons aged 10-69 years gives clinicians working with colour vision defects a possibility to estimate the normality or abnormality of the results in their patients.

Clinical features and a follow-up study in a family with X-linked progressive cone-rod dystrophy.

PURPOSE: To study a large family with X-linked progressive cone-rod dystrophy. METHODS: There were 128 members in the family. Of these, 45 had an ophthalmological examination and 3 gave their permission to use the results of their recent ophthalmological examination. In addition to the usual eye examination, visual fields, colour vision, dark adaptation and electroretinogram (ERG) were examined. RESULTS: Ten affected men aged 6 to 81 years were found in the family. The visual acuities varied from counting fingers (cf) 10 cm to 0.5 in the right eye (RE) and from cf 30 cm to 0.4 in the left eye (LE). The refraction was myopic in all affected members, varying from -1.5 to -24.0 D (RE) and from -2.0 to -20.25 D (LE). In visual functions, central scotomas and concentric constriction in the visual fields, red or red-green defects in colour vision, abnormal cone and rod dark adaptation and affected cone response in ERG were found. The 6 obligate carriers were aged 17 to 77 years. Their visual acuities varied from 0.05 (strabismic amblyopia) to 1.25(RE) and from 0.7 to 1.25 (LE), and refraction from +/-0 to +6.0 D (RE) and from -0.5 to +5.0 D (LE). Their visual fields and colour vision were normal. The non-affected men were aged 13 to 55 years, their visual acuity was normal in both eyes, and refraction varied from -5.0 to +1.5 D (RE) and from -5.5 to +1.75 (LE). The result of the eye examination was normal except in colour vision: two men were congenitally deuteranomalous. The women who were not obligate carriers were aged 10 to 77 years, their visual acuity was from 0.3 to 1.6 in both eyes, and refraction from -5.5 to +4.75 (RE) and from -5.25 to +4.0 (LE). Two women had one amblyopic eye. Otherwise the eye examination was normal. CONCLUSIONS: The clinical diagnosis of X-linked cone dystrophy 1 (COD1) is based on progressive loss of visual acuity, moderate or high myopia, red colour vision defect and affected cone response or cone and rod response in ERG. The future identification of the COD1 gene will confirm the diagnosis of the disease and help in genetic counseling of the family.

Adverse ocular effects of flecainide.

PURPOSE: To study if flecainide has ocular adverse effects. METHODS: Both eyes of 38 flecainide medicated patients were thoroughly examined including colour vision, contrast sensitivity and visual fields. RESULTS: 10.5% of the patients had blurred vision on lateral gaze lasting for a couple of seconds. Small corneal deposits were found in 14.5% of the patients. All visual function tests were normal. CONCLUSION: Flecainide seems to be a safe drug with minimal ocular adverse effects.

Normal values for the Pelli-Robson contrast sensitivity test.

PURPOSE: To define normal values for the Pelli-Robson contrast sensitivity test in different age groups. SETTING: University Eye Clinic of Kuopio, Kuopio, Finland. METHODS: Contrast sensitivity was measured with the Pelli-Robson contrast sensitivity test in 87 persons (60 women and 27 men) with a mean age of 34.5 years +/- 20.8 (SD) (range 6 to 75 years). Results were studied by age group (years): 6 to 9, 10 to 19, 20 to 29, 30 to 39, 40 to 49, 50 to 59, and 60 and older. Of 163 eyes, both were healthy in 76 persons and 1 was healthy in 11. Study participants consisted of members of the staff of the Kuopio University Hospital Eye Clinic, medical students at the Kuopio University, and patients of the Strabismus and General Ophthalmology Units of the Eye Clinic and their accompanying persons. Two test distances were used: 1 m and 3 m. Eyes were tested individually; thereafter, the test was done binocularly. RESULTS: There were significant differences in logarithmic contrast sensitivity values among the age groups except on the test of the left eye at 1 m. The P values for the right eye at 1 m and 3 m, left eye at 1 m and 3 m, and both eyes at 1 m and 3 m were 0.003, 0.002, 0.19, 0.043, 0.037, and 0.003, respectively. The mean test results in 1 eye varied from 1.68 in the 60 year and older group to 1.84 in the 20 to 29 and 30 to 39 year groups. Binocularly, the variation was from 1.73 in the 40 year group to 1.99 in the 30 year group. CONCLUSIONS: The Pelli-Robson contrast sensitivity test is a quick and reliable method in a clinical setting. Normal values of the test can be of help in evaluating cataract patients or patients having refractive surgery.

Color vision defects after central serous chorioretinopathy.

PURPOSE: To reexamine patients diagnosed with central serous chorioretinopathy (CSC) during the 10-year period from 1987 to 1996 to identify remaining color vision defects in the eyes with normal visual acuity (VA). METHODS: Thirty-nine patients were found with normal VA of 20/20 (logMAR 0) or better 8 to 166 months (mean +/- SD, 58.8 +/- 41.2) after active CSC. Color vision was examined with the Standard Pseudoisochromatic Plates part 2, Farnsworth-Munsell 100 hue test, and Color Vision Meter 712 anomaloscope. RESULTS: Of the CSC eyes, 26 (67%) had a color vision defect, most of them in the blue area. There was no correlation between the time since the active disease and the results on the color vision tests. Of the contralateral eyes, 19 (49%) also had a color vision defect. CONCLUSION: In many patients some degree of color vision defect remains after CSC even if the VA has recovered to normal. The contralateral eye can also have a color vision defect. This has not been previously reported and might be due to earlier subclinical CSC.

Central retinal artery occlusion after a local anesthetic with adrenaline on nasal mucosa.

The purpose of this article is to describe a 75-year-old patient with an acute central retinal artery occlusion after a local anesthetic with adrenaline on nasal mucosa. The local anesthetic was used in removing Jackson tubes from the left lacrimal canal. Occlusion of the central retinal artery related to nasal operations is a rare complication. In previous reports, retinal artery occlusions have been noted in connection with nasal submucosal injections of anesthetic and epinephrine. In our case, the use of anesthetic and adrenaline was superficial.

Build your own multipurpose, economically priced portable stereo microscope.

Binocular loupes and stereo microscopes are expensive items of equipment. However, inexpensive operating microscopes (ophthalmic) with coaxial illumination have been constructed for use in developing countries, where there is little medical funding. We describe one method of transforming economically priced pocket binoculars into a portable stereo microscope with nearly coaxial illumination.

Contrast and glare sensitivity in epilepsy patients treated with vigabatrin or carbamazepine monotherapy compared with healthy volunteers.

BACKGROUND/AIM: Many antiepileptic drugs have influence on visual functions. The aim of this study was to investigate possible changes in contrast sensitivity, macular photostress, and brightness acuity (glare) tests in patients with epilepsy undergoing vigabatrin (VGB) or carbamazepine (CBZ) monotherapy compared with healthy volunteers. METHODS: 32 patients undergoing VGB therapy, 18 patients undergoing CBZ therapy, and 35 healthy volunteers were asked to participate in an ophthalmological examination. In the previous study, visual field constrictions were reported in 40% of the patients treated with VGB monotherapy. In the present study, these VGB and CBZ monotherapy patients were examined for photopic contrast sensitivity with the Pelli-Robson letter chart and brightness acuity and macular photostress with the Mentor BAT brightness acuity tester. RESULTS: Contrast sensitivity with the Pelli-Robson letter chart showed no difference between these groups and normal subjects (ANOVA: p= 0.534 in the right eye, p= 0.692 in the left eye) but the VGB therapy patients showed a positive correlation between the contrast sensitivity values and the extents of the visual fields in linear regression (R = 0.498, p = 0.05 in the right eye, R = 0.476, p = 0. 06 in the left eye). Macular photostress and glare tests were equal in both groups and did not differ from normal values. CONCLUSION: The results of this study indicate that carbamazepine therapy has no effect on contrast sensitivity. Vigabatrin seems to impair contrast sensitivity in those patients who have concentrically constricted in their visual fields. Neither GBZ nor VGB affect glare sensitivity.

Color vision in epilepsy patients treated with vigabatrin or carbamazepine monotherapy.

PURPOSE: To investigate color vision in epilepsy patients treated with vigabatrin or carbamazepine monotherapy and to evaluate the association between vigabatrin-induced visual field defects and dyschromatopsia. DESIGN: Nonrandomized comparative trial. PARTICIPANTS: Thirty-two epilepsy patients treated with vigabatrin monotherapy, 18 patients treated with carbamazepine monotherapy, and 47 age-matched healthy controls were examined. MAIN OUTCOME MEASURES: Color vision was examined with Standard Pseudoisochromatic Plates 2 (SPP2) screening test, Farnsworth-Munsell 100 (FM 100) hue test, and Color Vision Meter 712 anomaloscope. RESULTS: Abnormal color perception was found in 32% of the epilepsy patients treated with vigabatrin monotherapy and 28% of the epilepsy patients treated with carbamazepine monotherapy. The total error score in the Farnsworth-Munsell 100 hue test was abnormally high in the vigabatrin monotherapy patients who had concentrically constricted visual fields and a statistically significant correlation was found between the temporal visual field extents and the age-adjusted Farnsworth-Munsell 100 total error score in vigabatrin monotherapy patients (R = .533, P = 0.003 in the right eye, R = .563, P = 0.001 in the left eye). Four of 31 (12%) vigabatrin monotherapy patients, and 1 of 18 (6%) carbamazepine monotherapy patients had a blue axis in Farnsworth-Munsell 100 hue test. In the anomaloscope, there were a few pathologic findings in both groups. In the SPP2 screening test, a few plates were not seen in both groups. CONCLUSIONS: Both examined antiepileptic drugs, vigabatrin and carbamazepine, cause acquired color vision defects. The abnormal color perception seems to be associated with constricted visual fields in the vigabatrin monotherapy patients. The duration of carbamazepine therapy correlates with high FM100 total error score. The best method for detecting dyschromatopsia in patients treated with vigabatrin or carbamazepine was the Farnsworth-Munsell 100 hue test. The SPP2 screening test does not seem to be useful in clinical practice.

Vigabatrin, a gabaergic antiepileptic drug, causes concentric visual field defects.

OBJECTIVE: To determine whether there is a causal link between vigabatrin treatment and concentric visual field defects and to evaluate the prevalence of these visual field constrictions. BACKGROUND: While the GABAergic antiepileptic drug (AED) vigabatrin was being clinically developed, only rare cases (less than 1:1000) of symptomatic visual field constriction and retinal disorders were reported. During 1997 to 1998, concentric visual field constrictions were described in case reports of mostly drug-resistant epilepsy patients receiving vigabatrin concurrently with other AEDs. METHODS: Ophthalmologic tests including Goldmann perimetry were performed on 32 adult patients on long-term successful vigabatrin monotherapy (treatment duration 29 to 119 months) and on 18 patients on carbamazepine monotherapy (treatment duration 32 to 108 months). Eighteen healthy adults served as controls. RESULTS: None of the patients complained about vision problems when asked to participate into the study. Thirteen out of the 32 (40%) epilepsy patients treated with vigabatrin monotherapy had concentrically constricted visual fields (9% severely, 31% mildly constricted), whereas none of the carbamazepine monotherapy patients or normal controls presented with a visual field defect (chi-square test, p = 0.0001). The extents of the visual fields were significantly constricted in vigabatrin group as compared with the visual fields of the patients in carbamazepine group or healthy controls (analysis of variance, Scheffe F-test, significant at 99%). CONCLUSIONS: The use of vigabatrin seems to increase the risk of a unique and specific pattern of bilateral, mainly asymptomatic visual field constriction. This risk should be considered when using vigabatrin. Visual field testing should also be performed before treatment and during routine follow-up for patients on vigabatrin.

Clinical features of Goldmann-Favre syndrome.

A 21-year-old woman complained of progressive loss of visual acuity. She had also had night blindness since she was ten years old. At the eye examination, the vitreous was found to be degenerated in both eyes. The fundus findings were a large retinoschisis in the right macula, edema resembling retinoschisis in the left macula and annular degenerative changes in the midperiphery. ERG and dark adaption were abnormal. This vitreoretinal degeneration was diagnosed as Goldmann-Favre syndrome.

Cataract in traffic.

BACKGROUND: To obtain a driver's licence to drive a private passenger car, the binocular visual acuity required is 0.5 or better, and the minimum horizontal width of the visual field is 120 degrees . Persons who fulfill these requirements can obtain a driver's licence even if they have an eye disease such as cataract. However, contrast sensitivity and visual acuity in glare can be considerably decreased in eyes with cataract, and this may create a risk factor in traffic. METHODS: Examinations of the eyes, visual fields, contrast sensitivity and glare sensitivity (visual acuity in glare and macular photostress test) were performed for 35 cataract patients aged 60 to 87 years (mean 70.1 years+/-6.1 SD). They had cataract in one or both eyes. In spite of the cataract, the visual acuity was > or =0.5 in 50 of the eyes. Twenty-two control eyes of persons within the same age range were similarly tested. RESULTS: The results in the contrast sensitivity test were significantly worse in the cataract eyes than in the control eyes. Contrast sensitivity decreased significantly as the visual acuity became worse. In the glare test, none of the control eyes lost any of the lines in the visual acuity chart. In the cataract eyes, the loss of lines with the highest glare varied from 0 to 6 lines (mean 1.4+/-1.5). The recovery time in the macular photostress test was longer, but not significantly, in cataract eyes than in normal eyes. There was no significant correlation between the loss of visual chart lines and visual acuity or between the recovery time in the macular photostress test and visual acuity. CONCLUSION: It would be advisable for traffic safety if simple tests for contrast and glare sensitivity were added to the requirements for a driver's licence, at least for older drivers. The age and test result limits should be defined.

Visual functions of drivers involved in traffic accidents.

Eye functions were studied in 56 drivers who had recently been involved in traffic accidents. There were 17 women and 39 men in the study group, aged 20-87 years. The traffic accidents had happened in intersections and city streets, in parking places and on highways. In seven drivers, a visual impairment was found: two drivers had strabismus and low visual acuities in one or both eyes, two had considerable hyperphoria, and three had a deutan color vision defect. However, comparing the type of accident to the defective eye functions showed no probable correlation.

Contrast sensitivity in patients recovered from central serous chorioretinopathy.

OBJECTIVE: To study contrast sensitivity in patients who have recovered from central serous chorioretinopathy (CSC). PATIENTS AND METHODS: Thirty-one patients who had recovered from CSC were examined with the Vistech and Pelli-Robson contrast sensitivity charts. The time from the onset of the active disease varied from 10 to 166 months (mean 60.4 +/- 42.0, SD). The visual acuity was 1.0 (logMar 0) or better. RESULTS: Contrast sensitivity of the affected eyes was significantly worse in the intermediate spatial frequencies of 3 and 6 cycles per degree (cpd) in the Vistech test compared to the fellow eyes (p = 0.032, 0.013, respectively). Contrast sensitivity of the affected eyes was significantly worse in all 5 spatial frequencies of the Vistech test and in the Pelli-Robson test compared to age-matched normal eyes (p = 0.006, 0.000, 0.000, 0.018, 0.000, 0.000, respectively). Contrast sensitivity of the fellow eyes was significantly worse in the spatial frequencies of 3 and 18 cpd in the Vistech test and in the Pelli-Robson test compared to age-matched normal eyes (p = 0.020, 0.019, 0.000, respectively). CONCLUSIONS: Contrast sensitivity does not seem to recover in all eyes after CSC even if the visual acuity has returned to normal. Therefore, contrast sensitivity testing is recommended for the patients complaining of visual impairment in spite of good visual acuity.

Visual function in professional truck drivers.

OBJECTIVES: The purpose of this study was to examine the visual function of professional truck drivers at working age to find out whether older drivers had any defective function and should therefore be given less demanding duties at work. METHODS: Of the 100 drivers invited to the study, 77 came to the examination, including 74 men and 3 women aged from 30 to 66 years (mean 50.3+/-10.3 years). In addition to the basic eye examination, visual fields, dark adaptation, contrast sensitivity, color vision, and glare sensitivity were studied. RESULTS: Two drivers (2.6%) had an incipient cataract in one eye, four (5.2%) had slight fundus abnormalities, five (6.5%) had exo- or esotropia, and five (6.5%) had amblyopia. Visual acuity in the better eye varied from 0.4 to 1.2 (mean 1.06+/-0.17) and in the other eye from 0.1 to 1.2 (mean 0.96+/-0.23). Five drivers (6.5%) had inadequate visual acuity for a professional driver's license. Visual fields were interpreted as normal in all drivers. The results of the dark-adaptation, contrast-sensitivity, and glare testing showed values within normal ranges for all drivers. In the color-vision tests, five male drivers (6.8% of the men) had a slight congenital green defect, and two drivers had an acquired blue defect in one eye because of cataract and diabetes. CONCLUSIONS: According to the present study, there is no need to give older drivers less demanding duties because of their eyes. However, one serious finding in the present study needs attention: the visual acuity was lower than that required for a professional driver's license in five drivers. Evidently, more regular checkups of visual acuity are needed for a professional driver's license.