Difficulty in performing everyday activities in patients with juvenile macular dystrophies: comparison with patients with retinitis pigmentosa

AIMS: To ascertain the level of perceived difficulty experienced by patients with central vision loss due to juvenile macular dystrophies in the performance of everyday activities. A second objective was to compare their perceived difficulty with that of patients with retinitis pigmentosa (RP) with primarily peripheral vision loss. METHODS: 72 patients with Stargardt disease, cone dystrophy, or cone-rod dystrophy who had visual acuities worse than 20/40 and normal peripheral visual fields rated themselves on their difficulty in the performance of 33 activities encompassing a wide variety of everyday tasks. These findings were compared with the responses of 120 patients with typical RP or Usher syndrome type 2 who had visual acuities of 20/40 or better and peripheral visual field loss. RESULTS: The juvenile macular dystrophy group reported the greatest level of overall self perceived difficulty with activities involving central vision, and lesser and variable degrees of difficulty with items within the mobility, negotiating steps, driving, and miscellaneous categories. Consistent with these findings, there were highly significant correlations between subjects' rated performances of activities involving central vision and the clinical measures of vision, including visual acuity and size of central scotoma. There were fewer significant correlations between perceived performance of activities in the other categories and the clinical measures. In general, those activities that showed significant correlations with the clinical measures of vision for the patients with juvenile macular dystrophies also showed significant differences in the patterns of responses between the juvenile macular dystrophy group and the RP group. Those items which were not correlated with the clinical measures in the juvenile macular dystrophy group tended not to show significant differences in the response patterns between the two groups. CONCLUSION: These results provide insight into the types of perceived difficulties in performing tasks of everyday life in patients with these disorders which affect counselling of these patients.     

Yearly rates of rod and cone functional loss in retinitis pigmentosa and cone-rod dystrophy

OBJECTIVE: To provide the first measures of the relative rates of rod and cone functional loss in patients with retinitis pigmentosa (RP) or cone-rod dystrophy (CRD). DESIGN: Five-year, prospective natural history study. PARTICIPANTS: Ninety-six patients (67 with RP and 29 with CRD) retaining measurable rod-mediated visual function and 5 normal subjects were tested at baseline and annually for 4 consecutive years. MAIN OUTCOME MEASURES: Tests of visual function included visual acuity, dark-adaptation thresholds, dark-adapted static perimetry, and rod and cone computer-averaged electroretinograms (ERGs), which were obtained over a range of retinal illuminances. Intervisit variability for each measure was obtained in a subset of patients who were tested twice within a 2-month interval and was used to determine whether an individual patient had shown progression, regression, or no change over a particular study interval. RESULTS: Over a 4-year interval, a significant number of patients with RP (60%) and CRD (62%) showed a decline in cone ERG amplitude. For rod ERG amplitude, the percentage of patients with RP or CRD showing progression was 64% and 45%, respectively. Although visual acuity, dark-adapted threshold, and rod visual field area also declined significantly over the 4-year period, the mean rate of change and the numbers of patients showing progression on these measures were lower than those for ERG measures. On specialized ERG testing, the yearly change in rod ERG threshold in RP was greater than the yearly change in cone ERG threshold, and the rate of progression varied significantly among inheritance types. For patients with CRD, the yearly change in rod threshold was comparable to the yearly change in cone ERG threshold. CONCLUSIONS: This study helps to define the natural progression of rod-mediated and cone-mediated functional loss in patients with RP and CRD.     

Study on treatment of retinitis pigmentosa with traditional Chinese medicine by Flicker electroretinogram

Study on treatment of 54 patients (106 eyes) of retinitis pigmentosa (RP) with traditional Chinese medicine was conducted by using modified method of electroretinography. Results showed: (1) Flicker response of electroretinogram was the most sensitive-criterion in examination, it was more effective when combined with infrared spectrogram. (2) The 30 Hz flicker index, response time were improved after TCM therapy in different hereditary types of RP, the improvement was significant in patients with Yang-Deficiency of Spleen-Kidney Syndrome and those of autosomal dominant inheritance type (P < 0.01). (3) Decrease of phase angle (phi) under different frequency of flicker after treatment was also significant statistically. The results suggested that flicker responses, which represents mainly retinal cone activity of patients, could be improved to a certain extent by TCM treatment, even in those with advanced retinal degeneration. TCM treatment could also enhance the bioactivity of nerve network and therefore have a definite significance in retarding the progression of disease and keeping the central vision. The flicker ERG, especially its flicker index, is an effective, sensitive and useful parameter for detection of visual function in patient with retinitis pigmentosa.     

Clinical picture and therapy of hypertrophic cardiomyopathy

Although central vision in Stargardt's disease is impaired relatively early, peripheral function is usually little affected and patients do not lose all vision. We report 4 patients with bull's-eye macular dystrophy that is indistinguishable from Stargardt's disease/fundus flavimaculatus, but with very depressed peripheral retinal function. One patient had bull's-eye maculopathy with a dark choroid on the fluorescein angiogram with a normal peripheral fundus and good retinal function initially. Sixteen years later, however, peripheral bone corpuscle pigmentation and optic disc atrophy developed and the electroretinogram became nonrecordable. Three patients from another family also had peripheral pigment degeneration besides macular degeneration. These cases may represent a rare combination of Stargardt's disease and retinitis pigmentosa. However, there was no clinical sign or even suggestion of retinitis pigmentosa at the initial examination in 1 patient. The mode of inheritance in 3 of our patients is probably autosomal recessive.     

Social ophthalmologic aspects of retinitis pigmentosa

Inherited retinal degenerations cause severe visual handicaps or blindness later in life. In typical rod cone dystrophy (retinitis pigmentosa) there is relevant visual loss in the third decade with implications for the patients' professional life, their mobility and their private life. For this reason, the disease is relevant for the individual patient as well as for society in general. We investigated social issues in 233 retinitis pigmentosa patients: 9.9% are not able to read any more; 40.9% have never had a driver's license and 27.8% quit driving because of a visual handicap. The mean reduction in the capacity for work is 86%; 12.7% are unable to work and therefore receive public financial support; 22.6% are unable to work in their profession; 20.9% are receiving public support because of legal blindness. Against this background it seems to be important that ophthalmologists inform their patients thoroughly about the implications of the disease for their professional and private lives. Doing this, he/she should ask for support from social service professionals.     

Asymmetry of retinitis pigmentosa-related to initial optic disc vasculitis

A case of highly asymmetric retinitis pigmentosa is reported. Signs of pigmentary retinopathy appeared in the first eye following optic disc vasculitis or neuroretinitis of unknown etiology. Within 2 years the visual field became markedly restricted and the dark adaptation thresholds elevated. Twelve years later this eye was almost blind and the ERG was non-recordable. In the fellow eye, the first pigmentary changes were observed 5 years after the initial presentation, and the progression was slow. Nineteen years after the initial examination the visual field of the less affected eye was constricted to 30 degrees nasally and 60 degrees temporally, the dark adaptation threshold was only slightly elevated, and the full-field ERG was within normal range. It is possible that neuroretinitis or vasculitis of the optic disc caused the earlier onset and the more progressive course of pigmentary retinopathy in the initially affected eye.     

Localization of CSNBX (CSNB4) between the retinitis pigmentosa loci RP2 and RP3 on proximal Xp

PURPOSE: Proximal Xp harbors many inherited retinal disorders, including retinitis pigmentosa (RP) and congenital stationary night blindness, both of which display genetic heterogeneity. X-linked congenital stationary night blindness (CSNBX) is a nonprogressive disease causing night blindness and reduced visual acuity. Distinct genetic loci have been reported for CSNBX at Xp21.1, which is potentially allelic with the RP3 gene, and at Xp11.23, which is potentially allelic with the RP2 gene. The study to identify the RP2 gene led to an extended study of families with potentially allelic diseases that include CSNBX. METHODS: Haplotype analysis of a family diagnosed with CSNBX was performed with 17 polymorphic markers on proximal Xp covering previously identified loci for CSNBX and XLRP. Two-point and multipoint lod scores were calculated. RESULTS: Informative recombinations in this family define a locus for CSNBX (CSNB4) with flanking markers DXS556 and DXS8080 on Xp11.4 to Xp11.3, an interval spanning approximately 5 to 6 cM. A maximum lod score of 3.2 was calculated for the locus order DXS556-1 cM-(CSNB4-DXS993)-2 cM-DXS1201. CONCLUSIONS: The results describe a new localization for CSNBX (CSNB4) between the RP2 and RP3 loci on proximal Xp. CSNB4 is not allelic with any previously reported XLRP loci; however, the interval overlaps the locus reported to contain the cone dystrophy (COD1) gene, and both diseases are nonrecombinant with DXS993. Because mutations in the RPGR gene to date account for disease in only a small proportion of RP3 families, the possibility that this new locus (CSNB4) also segregates with an as yet unidentified XLRP locus cannot be excluded.     

Human photoreceptor transplantation in retinitis pigmentosa. A safety study

OBJECTIVE: To establish the technical feasibility and safety of photoreceptor transplantation in retinitis pigmentosa. METHODS: A sheet of human photoreceptor cells was harvested from 2 human cadaveric eyes with a vibratome and transplanted into the subretinal spaces of 2 patients with advanced retinitis pigmentosa and visual acuity of no light perception by means of submacular surgery techniques. Preoperative and postoperative electrophysiologic testing, fundus photography, fluorescein angiography, and scanning laser ophthalmoscopy were performed. RESULTS: Twelve months after photoreceptor transplantation, the visual acuity of each patient remained no light perception. The temporal edge of the retinotomy in 1 patient was folded but was not associated with a retinal detachment. The patients were not immunosuppressed, and there was no evidence of rejection of the allogeneic transplant. Cystoid macular edema, uveitis, and macular pucker were not observed. CONCLUSION: A sheet of adult human photoreceptor cells can be harvested from human cadaveric eyes and safely transplanted to the subretinal spaces of patients with retinitis pigmentosa without systemic immunosuppression.     

Xanthogranulomatous pyelonephritis in a renal allograft recipient

PURPOSE: To describe the occurrence of Coats-like exudative retinopathy secondary to underlying retinitis pigmentosa in a 4-year-old child. METHOD: Case report. RESULTS: A 4-year-old girl had bilateral exudative retinal telangiectasia requiring photocoagulation. She subsequently developed progressive nyctalopia, photophobia, and reduced peripheral vision. Electroretinography and dark adaptometry at age 8 years confirmed the diagnosis of retinitis pigmentosa. CONCLUSIONS: Coats-like exudative retinopathy secondary to retinitis pigmentosa can manifest as early as age 4 years and can precede the diagnosis of the underlying retinal dystrophy.     

A new codon 15 rhodopsin gene mutation in autosomal dominant retinitis pigmentosa is associated with sectorial disease

OBJECTIVE: To ascertain and characterize rhodopsin gene mutations in autosomal dominant retinitis pigmentosa and to correlate these mutations with the clinical phenotypes. METHODS: DNA was extracted from leukocytes, and the rhodopsin gene was amplified and analyzed using molecular-biological methods. Clinical and electrophysiological data were collected from patient charts. RESULTS: We found a disease-causing mutation that was previously undescribed, to our knowledge, for autosomal dominant retinitis pigmentosa within codon 15 of exon 1 of the rhodopsin gene. It was a single base-pair transversion (AAT to AGT) leading to a serine-for-asparagine substitution. This altered a glycosylation site in the intradiscal portion of the rhodopsin molecule. The pedigree examined demonstrated an inferior distribution of retinal pigmentary changes and predominantly superior visual field loss with relative preservation of electroretinographic amplitudes and good vision, which is consistent with sectorial or sectorial-like retinitis pigmentosa. CONCLUSIONS: A codon 15 rhodopsin gene mutation caused retinitis pigmentosa in the pedigree studied. There may be an association between intradiscal rhodopsin gene mutations and sectorial forms of retinitis pigmentosa.     

Analysis of ERG a-wave amplification and kinetics in terms of the G-protein cascade of phototransduction

PURPOSE: To test rigorously the hypothesis that the a-wave of the electroretinogram (ERG) is proportional to the rod photocurrent by examining the applicability to a-waves of a recent model of the activation steps in the G-protein cascade of phototransduction. METHODS: ERGs were recorded in response to flashes of graded intensity, from six dark-adapted normal subjects and from two patients, one with retinitis pigmentosa (RP) and one with cone retinal dystrophy with rod involvement (CRD). The a-wave portions of the responses were analyzed with a model of the activation steps of the G-protein cascade. The model is characterized by a parameter, A, the amplification constant, with units of s-2 (per photoisomerization), which may be expressed as the product of physical and biochemical parameters of the transduction cascade. RESULTS: Each a-wave family was well described by the model. For the six normal subjects, we obtained A approximately 7 s-2, about 100-fold greater than in isolated amphibian rods at 22 degrees C, but close to the value for isolated primate rods. For the patient with RP, the maximum a-wave amplitude (amax) was considerably reduced, but the amplification constant was normal (A = 7.5 s-2). In contrast, the patient with CRD had a nearly normal amax but had an amplification constant about sixfold lower than normal (A = 1.1 s-2). CONCLUSIONS: The authors conclude that the a-wave is a direct reflection of the rod photo-current and that the rising phase kinetics are accurately described by a simple model of the G-protein cascade. They show that the small volume of the human rod outer segment is crucial to the achievement of high amplification, and they show how their observations constrain the possible pathologies of phototransduction in patients with retinal disease.     

X-linked retinitis pigmentosa in two families with a missense mutation in the RPGR gene and putative change of glycine to valine at codon 60

OBJECTIVE: This study describes the ophthalmic findings in two unrelated white families with X-linked retinitis pigmentosa (XLRP) caused by a missense mutation in the retinitis pigmentosa GTPase regulator (RPGR) gene. DESIGN: Genetic screening and clinical correlation. PARTICIPANTS: Thirty-six families with XLRP seen by the authors were screened for a possible mutation in the RPGR gene to identify three affected hemizygotes with retinitis pigmentosa and four heterozygote carriers in one family and one hemizygote and one carrier in a second family. INTERVENTION: All nine patients underwent a routine ocular examination, including slit-lamp biomicroscopy and a dilated fundus examination. Goldmann visual field kinetic perimetry, static threshold perimetry, and electroretinography also were obtained. The DNA screening was performed on the three affected male patients and four obligate carriers examined from one family and the two examined patients, plus an additional male and obligate carrier, from the second family to determine the presence of any causative mutation in the RPGR gene. MAIN OUTCOME MEASURES: Findings on fundus examination, static threshold and kinetic perimetry, and electroretinography testing were the main outcome measures. RESULTS: A G-->T nucleotide change at position 238 in exon 3 of the RPGR gene resulting in a putative substitute of Gly-->Val at codon 60 was shown to segregate with RP in affected males and the carrier state in female heterozygotes in these two families. The ophthalmologic findings in hemizygotes as well as the carriers in this family were within the spectrum of findings characteristically noted in XLRP families. A tapetal-like reflex was not observed in any of the five female carriers. Psychophysical and electrophysiologic testing on the carriers indicated that cone and rod functions were impaired equivalently. When present in the carriers, visual field restriction was most apparent in, or limited to, the superotemporal quadrant, which corresponded to the retinal pigmentary changes that tended to occur in the inferonasal retina. CONCLUSIONS: A mutation in exon 3 of the RPGR gene, which would result in a putative glycine to valine substitution at codon 60, is associated with a severe clinical phenotype in male patients and a patchy retinopathy without a tapetal-like reflex in carrier females. In these families, heterozygote carriers showed equivalent impairment of their cone and rod function.     

A c-rasHa mutation in the metastasis of a human papillomavirus (HPV)-18 positive penile squamous cell carcinoma suggests a cooperative effect between HPV-18 and c-rasHa activation in malignant progression

Progressive X-linked cone-rod dystrophy (COD1) is a retinal disease affecting primarily the cone photoreceptors. The COD1 locus originally was localized, by the study of three independent families, to a region between Xp11.3 and Xp21.1, encompassing the retinitis pigmentosa (RP) 3 locus. We have refined the COD1 locus to a limited region of Xp11.4, using two families reported elsewhere and a new extended family. Genotype analysis was performed by use of eight microsatellite markers (tel-M6CA, DXS1068, DXS1058, DXS993, DXS228, DXS1201, DXS1003, and DXS1055-cent), spanning a distance of 20 cM. Nine-point linkage analysis, by use of the VITESSE program for X-linked disorders, established a maximum LOD score (17.5) between markers DXS1058 and DXS993, spanning 4.0 cM. Two additional markers, DXS977 and DXS556, which map between DXS1058 and DXS993, were used to further narrow the critical region. The RP3 gene, RPGR, was excluded on the basis of two obligate recombinants, observed in two independent families. In a third family, linkage analysis did not exclude the RPGR locus. The entire coding region of the RPGR gene from two affected males from family 2 was sequenced and was found to be normal. Haplotype analysis of two family branches, containing three obligate recombinants, two affected and one unaffected, defined the COD1 locus as distal to DXS993 and proximal to DXS556, a distance of approximately 1.0 Mb. This study excludes COD1 as an allelic variant of RP3 and establishes a novel locus that is sufficiently defined for positional cloning.     

Neurobiology of retinal dopamine in relation to degenerative states of the tissue

Neurobiology of retinal dopamine is reviewed and discussed in relation to degenerative states of the tissue. The Introduction deals with the basic physiological actions of dopamine on the different neurons in vertebrate retinae with an emphasis upon mammals. The intimate relationship between the dopamine and melatonin systems is also covered. Recent advances in the molecular biology of dopamine receptors is reviewed in some detail. As degenerative states of the retina, three examples are highlighted: Parkinson's disease; ageing; and retinal dystrophy (retinitis pigmentosa). As visual functions controlled, at least in part, by dopamine, absolute sensitivity, spatial contrast sensitivity, temporal (including flicker) sensitivity and colour vision are reviewed. Possible cellular and synaptic bases of the visual dysfunctions observed during retinal degenerations are discussed in relation to dopaminergic control. It is concluded that impairment of the dopamine system during retinal degenerations could give rise to many of the visual abnormalities observed. In particular, the involvement of dopamine in controlling the coupling of horizontal and amacrine cell lateral systems appears to be central to the visual defects seen.     

Assessment of local retinal function in patients with retinitis pigmentosa using the multi-focal ERG technique

To assess local retinal function in patients with retinitis pigmentosa (RP), multi-focal ERGs and local thresholds (static visual fields) were obtained on eight RP patients with visual acuities of 20/25 or better. All eight patients showed multi-focal responses with normal timing within the central 5 deg. However, there were few responses with normal timing in the areas outside the central 7.5 deg, except in the case of the only patient with a 30 Hz full-field response with normal timing. Since full-field ERGs are dominated by responses from the periphery, this finding supplies a foundation for the commonly observed delays in the full-field cone ERGs of patients with RP. With respect to amplitude, only two patients showed multi-focal responses with near normal amplitudes anywhere in the field. The loss of amplitude at any point was not a good predictor of visual sensitivity in the Humphrey visual field. On the other hand, all areas with normal timing had near normal sensitivity. Timing changes appear to be an early indication of local retinal damage to the cone system. Nearly all areas with sensitivity losses greater than 0.5 log unit, and some areas with near normal sensitivity, showed significantly delayed multi-focal ERGs. Finally areas with extreme sensitivity loss show multi-focal responses with a wide range of amplitudes and implicit times across patients, suggesting different mechanisms of disease action in different patients.     

Attachment of Burkholderia pseudomallei to pharyngeal epithelial cells: a highly pathogenic bacteria with low attachment ability

OBJECTIVE: To identify the mutation in a human transforming growth factor beta-induced gene (BIGH3) in a Japanese family with a severe form of granular corneal dystrophy of early onset associated with recurrent corneal erosions. PATIENTS: The tentative clinical diagnosis in this family was Reis-Bücklers corneal dystrophy; 4 persons affected with this disorder have been identified in 4 generations, and 3 of the 4 were examined. The proband underwent keratoplasties in our hospital (Keio University Hospital, Tokyo, Japan). METHODS: The BIGH3 gene was examined for a mutation by the polymerase chain reaction and direct sequencing. Corneal buttons of the proband were stained and examined by electron microscopy. RESULTS: Three affected persons were shown to have a heterozygous G-->T transversion at the second nucleotide position of codon 124 (Arg-->Leu) of the BIGH3 gene. In the proband, corneal deposits between the epithelium and the Bowman layer stained red with Masson trichrome stain. Electron microscopy revealed numerous electron-dense, rod-shaped bodies next to the epithelial basement membrane but no curly fibers suggestive of Thiel-Behnke dystrophy. CONCLUSION: A novel R124L mutation of the BIGH3 gene was associated in this family with a superficial variant of granular corneal dystrophy. CLINICAL RELEVANCE: This mutation causes a severe form of superficial granular corneal dystrophy by producing abnormal keratoepithelin between the epithelium and the Bowman layer and thus clinical similarities to Reis-Bücklers corneal dystrophy.     

Evaluation of the Night Vision Spectacles on patients with impaired night vision

BACKGROUND: The Night Vision Spectacles (NiViS) were developed by a consortium of European companies to assist individuals who suffer from impaired night vision. They consist of a head-mounted video camera (input) and binocular displays (output) connected to a portable computer processor, which uses an algorithm to enhance the luminance and contrast of the video image. METHODS: Eighteen patients with impaired night vision were tested, including those with retinitis pigmentosa (7), Usher syndrome (2), fundus albipunctatus (1) and complete (4) and incomplete (4) congenital stationary night blindness. Normal trichromats (3) and typical, complete achromats (2) acted as controls. A battery of tests assessed: visual acuity at 5 m (projection unit) and 1 m (chart) and at high and low contrasts; contrast sensitivity; absolute and increment threshold; the influence of glare; contrast motion detection; and hand-eye performance. The tests were performed, with and without the NiViS, at three adaptation levels: low scotopic (10(-3) cd/m2), high scotopic (10(-2) cd/m2) and mesopic (10(-1) cd/m2). RESULTS: At the low and high scotopic levels, the majority of patients showed improved performance on the visual acuity, contrast sensitivity and motion contrast tests with the NiViS. At the mesopic level, the advantage with the NiViS was greatly reduced, but still present for contrast sensitivity. CONCLUSION: Patients with impaired night vision can benefit from the NiViS when performing tasks involving contrast and motion perception. Those with normal visual fields and retaining good photopic vision will benefit more than those with constricted visual fields and impaired cone vision. Recommendations regarding desirable improvements of the NiViS and suitability for the individual patient are given.     

Retinitis pigmentosa inversa

BACKGROUND: Retinitis pigmentosa (RP) is one of the most common inherited retinal diseases, with a prevalence of about 1 in 3500 to 4500. Retinitis pigmentosa inversa is a rare variant of this disorder characterized by areas of choroidal degeneration with pigment migration and bony spicule formation in the macular area. In contrast to more typical forms of RP, this anomaly destroys central vision, leaving peripheral vision intact. CASE REPORT: A 47-year-old white male was followed for about 7 years with evidence of progressive retinal pigment epithelial atrophy and hyperpigmentation affecting both maculae. Since 1970, he had noted difficulty seeing at night as well as an acquired hearing deficit that appeared to be getting worse, ultimately impairing his ability to safely drive a truck. Medical history was positive for either chloroquine or hydroxychloroquine use for 2 to 3 years as malaria prophylaxis while he served in Vietnam. In addition, his father in Louisiana had visual loss of unknown cause. During the 7-year period, the condition progressed rapidly. The patient became virtually blind secondary to visual acuity loss with dense central and paracentral scotomas. The peripheral visual fields remained intact. After several years of extensive examinations, including laboratory, electroretinography, and genetic testing, a definitive diagnosis of RP inversa was made. DISCUSSION: RP inversa is a rare form of tapetoretinal degeneration that is characterized by decreased central vision with normal peripheral vision. A recessive form of inheritance has been postulated but never substantiated. Although there is currently no treatment, recent studies have indicated that 15,000 IU of vitamin A palmitate daily may slow the progression of retinitis pigmentosa; however, it is unknown whether this treatment would be effective for the inverse form of RP. Differential diagnoses include Leber's congenital amaurosis, central gyrate atrophy, central areolar choroidal sclerosis, progressive cone-rod dystrophy, syphilitic retinopathy, retinal toxicity from phenothiazine use, and chloroquine/hydroxychloroquine retinopathy.     

Severe hereditary retinal diseases in childhood

In dependence on the various statistics, hereditary causes are identified in up to 50% of the visually handicapped and blind school children. Most common are retinal disorders, which account for 15 to 55%. The most important diseases are briefly reviewed: Leber's congenital amaurosis, rod monochromacy, blue cone monochromacy, congenital stationary night blindness (CSNB), X-linked retinitis pigmentosa, Usher syndromes, Bardet-Biedl syndrome, juvenile neuronal ceroid lipofuscinosis Spielmeyer-Vogt, the various forms of albinism, exsudative vitreoretinopathies including Norrie's disease, as well as Stargardt's macular dystrophy, vitelliform macular dystrophy, and hereditary retinoblastoma. In addition to the clinical symptoms, general genetic principles are stressed, such as mode of inheritance, heterogeneity, expressivity, penetrance, age at manifestation, X-chromosomal gene inactivation, and variability. They all have to be taken into account to correctly establish the diagnosis, to identify family members at risk, and to provide adequate genetic counselling. An overview of the actual molecular genetics of the various retinal disorders is also given.