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.

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.

Changes of refraction in schoolchildren.

The refractions of 1,118 children, aged 7 to 15 years, were followed for one to eight years; 260 children were hyperopic and 828 were myopic throughout the observation time. Thirty additional hyperopic children became myopic during follow-up. In the cross-sectional study, the mean annual change of refraction in hyperopic children varied from -0.03 to -0.11 diopters in different age groups. In myopic children, the variation was from -0.46 to -0.93 D. In the longitudinal follow-up study (from five to eight years), the mean annual change of refraction in hyperopic children was -0.12 D compared with -0.55 D in myopic children. The mean annual change in the 30 hyperopic children who became myopic was -0.21 D while hyperopic and -0.60 D while myopic. The difference is highly significant. It clearly shows that the changes of refraction in hyperopic schoolchildren occur much more slowly than in myopic children of the same age.

Ocular side effects of amiodarone.

Amiodarone is an effective antiarrhythmic agent. During therapy, intracytoplasmic lamellar deposits occur in the cornea, lens, retina, and optic nerve. The most common symptom, reported by 1.4-40.0% of patients, is colored rings around lights. The most common ocular finding is corneal epithelial opacities resembling a cat's whiskers in 70-100% of patients; however, lens opacities have been reported in 50-60% of patients. Neither type of deposit impairs visual acuity, and their presence is not contraindicative to continued amiodarone treatment. Retinopathy has, rarely, been reported in association with amiodarone treatment. Optic neuropathy in patients receiving the drug for various lengths of time has been reported as having incidences of 1.3% during the preceding 8 years and 1.76% during the preceding 10 years. Although a causal relationship is not well established, if optic neuropathy is observed, discontinuing or reducing the medication, if not life threatening, should be considered.

Colour vision and dark adaptation in high myopia without central retinal degeneration.

Colour vision and dark adaptation of 36 high myopes (68 eyes) without degenerative fundus changes were studied with the standard pseudoisochromatic plates part 2, Farnsworth-Munsell 100 hue (FM 100) test, Nagel anomaloscope, colour vision meter 712-anomaloscope, and Goldmann-Weekers adaptometer. The ages of the myopes ranged from 20 to 49 years, the visual acuity from 6/12 to 6/6, and the refractions from -6.0 to -20.0 D. All the colour vision tests and dark adaptation examination gave normal results. However, the error scores of the myopes in (blue) box III of the FM 100 test were significantly higher than those of the controls matched for age. In dark adaptation, the rod thresholds of the myopes were significantly higher than in the controls. The stretching of the posterior pole of the eye might explain this minimal impairment of the photoreceptor layer of the retina without any visible degenerative changes in the fundus.

Colour vision in gyrate atrophy.

A follow-up study of colour vision in two patients with gyrate atrophy was performed. Gyrate atrophy was diagnosed in the first patient at the age of 17 years. Her colour vision was first tested at the age of 25 years; at the follow-up examination 7 years later, she correctly interpreted the Standard Pseudoisochromatic Plates part 2, however, with one mistake due to lens opacity. In the Farnsworth-Munsell 100 hue test and in the Color Vision Meter 712 (CVM) anomaloscope, the results were within normal ranges. In the second patient, gyrate atrophy was diagnosed at the age of 4 years. At the ages of 4 and 5 years, he correctly interpreted the Ishihara, AO H-R-R, and Lanthony Tritan Album plates as well as the City University test. At the ages of 6, 7, and 8 years, he correctly interpreted the plate tests, the Farnsworth Panel D 15, and Lanthony's Desaturated Panel. The CVM anomaloscope results were normal.

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.

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 in patients with a silicone intraocular lens.

PURPOSE: To test color vision in eyes with a silicone intraocular lens (IOL) and compare it with that in normal phakic eyes. SETTING: University Eye Clinic of Kuopio, Finland. METHODS: Color vision in 33 patients from 50 to 69 years old with a silicone IOL was evaluated with the Farnsworth-Munsell 100 hue test (FM 100) and the Color Vision Meter 712 (CVM) anomaloscope. In the FM 100 test, 37 normal phakic eyes served as controls; 21 were 50 to 59 years old and 16, 60 to 69 years old. In the CVM, 46 normal phakic eyes served as controls; 21 were 50 to 59 years old and 25, 60 to 69 years old. Nine of the 33 patients had a silicone IOL in one eye and a poly(methyl methacrylate) (PMMA) IOL in the other; the color vision in the two eyes was compared. RESULTS: The FM 100 results showed no significant difference between the silicone IOL and control eyes. In the CVM examination, the blue equation showed a significantly greater shift to the green side (patient sees more blue) in the silicone IOL group than in the control group. Other CVM results were similar between groups. No significant difference was found in any test between the 9 PMMA IOL eyes and the contralateral silicone IOL eyes. CONCLUSION: Eyes with a silicone IOL had color discrimination ability similar to that of normal phakic eyes. In the blue color sensitivity test, the silicone IOL eyes had significantly better results. There were no significant differences between eyes with a silicone IOL and contralateral eyes with a PMMA IOL.

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.

Predicting of myopia progression in school children.

Myopia in 214 school children has been followed from one to nine years. The children have been divided in groups according to the age of onset of myopia and the amount of final myopia at the age of 15 or 16 has been recorded. If myopia started before puberty (at the age of 10 or younger) 70% of the children ended up with myopia of -3.0 to -5.75 D, only 12.5% remained under -3.0 D, and 17.5% had myopia -6.0 D or more. If myopia began at the ages of 11-15, 66.7% remained under -3.0 D, 32.2% reached -3.0 to -5.75 D, and only 1.1% of the children had myopia of -6.0 D or more. Of all the 214 children, 95.8% had myopia less than -6.0 D at the age of 15-16 years. However, the individual variation is very wide, and it is difficult to predict the final amount of myopia in school years in an individual case.

The amblyopic schoolgirl syndrome.

The occurrence of psychogenic amblyopia in a population of school children was studied. From the population of 14,000 school children under the surveillance of school nurses and doctors, 2280 were referred to the author for an ophthalmological examination during a two-year period. Forty children (1.75%) were diagnosed as having psychogenic amblyopia corresponding to an incidence of 1.4/1000/year. Psychogenic amblyopia was characterized by a high percentage of girls (48 out of 52) and the highest occurrence at the age of 9 to 11 years. There was a wide variation of the duration of the condition, but 37% of the patients recovered within one year. A psychological cause for amblyopia could be revealed in only a few cases. According to the present study psychogenic amblyopia can occur at a relatively high incidence. Awareness of this condition could spare these children from straining, expensive tests.

Accommodation in hyperopic and myopic school children.

Binocular accommodation of 150 consecutive hyperopic and 150 myopic school children was measured during the eye examination. There were 99 girls and 51 boys in the hyperopic group and 100 girls and 50 boys in the myopic group. The ages varied from seven to 16 years. Accommodation of the hyperopic children varied from 4 to 20 D (mean 10.6 +/- 3.4), and in the myopic children also from 4 to 20 D (mean 10.9 +/- 2.5). The difference between these means was not statistically significant. However, hyperopic girls aged 12 to 16 years showed low values of accommodation (mean 9.0 +/- 2.7) compared to the other corresponding age groups. In the second part of the study the refraction of 80 children, aged seven to 15 years, with decreased accommodation was studied retrospectively to see if they had a tendency to become myopic. The follow-up time was from one to eight years, and the accommodation at the beginning of the observation time varied from 2 to 7 D. The mean annual change of the refraction of these children was from -0.03 to -0.17 D. In 34 children there was no change at all, and in 12 children the change of refraction was slightly toward more hyperopia. Only three of these 80 children became myopic during the observation time. This incidence is lower than the incidence of myopia at these ages. Thus, accommodative power of hyperopic and myopic school children appears to be on the same level, and low accommodation does not predict the development of myopic refraction in the school years.

Accommodation in school children with music or sports activities.

The accommodation of 324 school children aged 10 to 16 years was studied before and after a 12-minute reading session. One hundred and twenty children (81 girls and 39 boys) were wind instrument players in school bands, 93 children (48 girls and 45 boys) trained in an individual sport, and 111 children (65 girls and 46 boys) having no such activities were studied as a control group. At the end of the reading session, decreased accommodation (7 diopters or less) was found in 19 (15.8%) of the musicians, in six (6.5%) of the athletes, and in six (5.4%) of the control group. The difference was significant between the musicians and the control group, but not significant between the athletes and the control group. The majority of the children with low accommodation were girls; there was only one boy with decreased accommodation in each of the three groups.

Color vision in diabetic school children.

The color vision of 64 diabetic school children was studied. Acquired color vision defects due to diabetes could not be found in any of the children. Two of the children had a congenital red-green color vision defect. In the examination, three different pseudoisochromatic plate tests (Isihara, Standard Pseudoisochromatic Plates part 2, and Lanthony Tritan Album) were used as well as the Nagel anomaloscope and three different cap arrangement tests (Panel D 15, Lanthony Desaturated Panel, and Farnsworth-Munsell 100 hue). The plate tests and the anomaloscope examination were fast, reliable, and well accepted by the children. The cap arrangement tests took more time, and many of the children neither liked nor properly performed these tests. Twelve color dependent glucose strip tests for diabetes care at home were also studied. A few of the youngest school children made mistakes in interpreting the colors of these strips, although their color vision was normal.

Observations on the use of three different contrast sensitivity tests in children and young adults.

Forty-one children and young adults aged 4 to 25 years (mean 14.5 +/- 6.9, SD) with normal eyes were examined with three different contrast sensitivity tests: the Vistech distance and near test, the Cambridge Low Contrast Gratings test, and the LH-5 Contrast test. In different age groups, the youngest children aged 4 to 9 years had the lowest result values. The results of the older children aged 10 to 15 years and young adults aged 16 to 25 years were close to each other. The range of the results in all tests was large in every age group. The values of contrast sensitivity could not be compared from one test to another; in the Vistech tests the values varied from 10 to 200, in the Cambridge test from 170 to 560, and in the LH-5 test from 5 to 50. Most of the children liked the LH-5 test best, while most of the young adults preferred the Vistech distance test. It is useful to examine children and adults with different contrast sensitivity tests; however, the same test should be used in follow-up examinations.

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.