[Diagnosis of retinal diseases. Comparison between multifocal ERG and fundus perimetry - a case study]. / Diagnostik bei Netzhauterkrankungen Vergleich von multifokalem ERG und funduskontrollierter Perimetrie - Fallstudie.

BACKGROUND: There are new methods available for function testing of the macula, i.e. multifocal Electroretinography (mfERG) as well as fundus perimetry with the scanning laser ophthalmoscope (SLO). The value and clinical impact of these methods have still to be evaluated. We wanted to compare the results from patients having undergone both examinations. PATIENTS AND METHODS: A total of 33 eyes from 25 patients (visual acuity 0.03-0.8) aged 14-79 years were examined using fundus perimetry with the SLO. In addition, multifocal ERG was performed in all eyes, where 61 local ERGs inside the 30 degrees visual field were recorded. We compared the depth of the scotoma with the reduction of the amplitudes during mfERG taking the fixation status into consideration. RESULTS: Examination time was comparable for both examination techniques. There was good concordance for eyes with retinitis pigmentosa with only central response. In contrast, patients with juvenile macular dystrophy demonstrated different results with comparable size of the defect while sometimes an enlarged pathology during mfERG was observed. Correlation between pathology findings observed in mfERG and fundus changes was difficult due to the change of the point of fixation caused by central scotoma. In age-related macular degeneration correlation of the findings was less obvious. DISCUSSION: The different setting with supra-threshold stimuli during ERG in contrast to near-threshold stimulus presentation during perimetry, might be the reason for differences even in the beginning of retinal diseases. In addition, reduced stability of fixation leads to artifacts during mfERG while it may be compensated for in fundus perimetry. Both methods are of additional value and demonstrate different results depending on the disease.

[Satisfaction with low vision aids]. / Nutzung und Akzeptanz von vergrössernden Sehhilfen.

PURPOSE: To study satisfaction with the prescription of low vision aids (LVA) and to correlate LVA with eye disease and visual function one year after prescription. METHODS: A questionnaire was sent out to 576 patients who had received LVAs in 1998. We evaluated their subjective satisfaction with the LVA as well as with the whole examination in our low vision department and compared the kind of LVA with disease and visual acuity. In addition, we observed whether additional functional deterioration led to problems with the LVA. RESULTS: 301 questionnaires were returned (52 %). They reported on high satisfaction with the management and the LVA (> 90 %). 57 % used their optical LVAs more than 5 times daily mostly for reading and writing (74 % and 78 %, respectively). However, 20 patients were no longer able to read with their LVA due to decrease of function. When comparing the LVAs, most patients with age-related macular degeneration were supplied with magnifiers (30 %). Thirty percent of the patients supplied with CCTVs (43 %; visual acuity 0.02 to 0.3) used the CCTV daily. CONCLUSIONS: The majority of low vision patients is very satisfied with the prescription of LVAs and frequently uses these aids. The adequate LVA is a major factor improving the quality of life. However, due to the possibility of greater deterioration after the disease, follow-up examinations on a regular basis appears to be necessary. The early prescription of CCTVs often helps to preserve the reading ability and should therefore be kept in mind by the physician dealing with low vision patients.

Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene.

Mutations in the crumbs homologue 1 (CRB1) gene cause a specific form of retinitis pigmentosa (RP) that is designated "RP12" and is characterized by a preserved para-arteriolar retinal pigment epithelium (PPRPE) and by severe loss of vision at age <20 years. Because of the early onset of disease in patients who have RP with PPRPE, we considered CRB1 to be a good candidate gene for Leber congenital amaurosis (LCA). Mutations were detected in 7 (13%) of 52 patients with LCA from the Netherlands, Germany, and the United States. In addition, CRB1 mutations were detected in five of nine patients who had RP with Coats-like exudative vasculopathy, a relatively rare complication of RP that may progress to partial or total retinal detachment. Given that four of five patients had developed the complication in one eye and that not all siblings with RP have the complication, CRB1 mutations should be considered an important risk factor for the Coats-like reaction, although its development may require additional genetic or environmental factors. Although no clear-cut genotype-phenotype correlation could be established, patients with LCA, which is the most severe retinal dystrophy, carry null alleles more frequently than do patients with RP. Our findings suggest that CRB1 mutations are a frequent cause of LCA and are strongly associated with the development of Coats-like exudative vasculopathy in patients with RP.

A new clinical classification for Usher's syndrome based on a new subtype of Usher's syndrome type I.

OBJECTIVES: Usher's syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss and progressive visual loss secondary to retinitis pigmentosa. Usher's syndrome is both clinically and genetically heterogeneous. Three clinical types are known today. METHODS: We conducted a study on 74 patients with Usher's syndrome, performing complete audiological and neurotological examinations. RESULTS: Twenty-six patients had total profound hearing loss and retinitis pigmentosa (Usher's syndrome type I), and 48 patients had moderate to severe sensorineural hearing loss and retinitis pigmentosa (Usher's syndrome type II). We identified 9 of the 26 Usher's syndrome patients with profound hearing loss who showed a normal response to bithermal vestibular testing. CONCLUSIONS: The combination of profound hearing loss and normal response to bithermal vestibular testing has not been previously described in Usher's syndrome. Therefore we describe a new subtype of Usher's syndrome type I and suggest a modified clinical classification for Usher's syndrome.

[Utilization of a new night vision enhancement device (DAVIS)]. / Einsatz einer neuen Nachtsichtbrille (DAVIS).

PATIENTS AND METHODS: Following complete ophthalmologic examination 37 patients with night blindness due to Retinitis Pigmentosa (sometimes Usher-Syndrome) and Choroideremia (n = 3) performed several tests with DAVIS during darkness. We evaluated the improvement of visual function on a special outside course in the city of Heidelberg (duration 1.5 to 4 hours). RESULTS: Twenty six of the patients were able to better recognize obstacles, 28 could see objects which were not seen without DAVIS. Twenty two of the 37 patients would use the DAVIS. Patients needed a visual acuity of more than 0.1 and more than 6 degree of central visual field to experience improvement with DAVIS. However, in patients with only minimal changes of the visual field, the restriction due to the presence of the device was a drawback. Sudden occurrence of light sources leads to blinding and limits the indoor use. CONCLUSION: DAVIS enhances contrast acuity especially during night and twilight. This leads to improvement of orientation due to better recognition of obstacles and allows rehabilitation of patients with night blindness for outdoor mobility. Individual test and adjustment of DAVIS is necessary to allow exact and adequate prescription.

Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy.

The photoreceptor cell-specific ATP-binding cassette transporter gene (ABCA4; previously denoted "ABCR") is mutated, in most patients, with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of AR CRD, we selected 5 patients with AR CRD and 15 patients from Germany and The Netherlands with isolated CRD. Single-strand conformation-polymorphism analysis and sequencing revealed 19 ABCA4 mutations in 13 (65%) of 20 patients. In six patients, mutations were identified in both ABCA4 alleles; in seven patients, mutations were detected in one allele. One complex ABCA4 allele (L541P;A1038V) was found exclusively in German patients with CRD; one patient carried this complex allele homozygously, and five others were compound heterozygous. These findings suggest that mutations in the ABCA4 gene are the major cause of AR CRD. A primary role of the ABCA4 gene in STGD1/FFM and AR CRD, together with the gene's involvement in an as-yet-unknown proportion of cases with AR RP, strengthens the idea that mutations in the ABCA4 gene could be the most frequent cause of inherited retinal dystrophy in humans.

Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration.

Recently, the VMD2 gene has been identified as the causative gene in juvenile-onset vitelliform macular dystrophy (Best disease), a central retinopathy primarily characterised by an impaired function of the retinal pigment epithelium. In this study we have further characterised the spectrum of VMD2 mutations in a series of 41 unrelated Best disease patients. Furthermore we expanded our analysis to include 32 unrelated patients with adult vitelliform macular dystrophy (AVMD) and 200 patients with age-related macular degeneration (AMD). Both AVMD and AMD share some phenotypic features with Best disease such as abnormal subretinal accumulation of lipofuscin material, progressive geographic atrophy and choroidal neovascularisation, and may be the consequence of a common pathogenic mechanism. In total, we have identified 23 distinct disease-associated mutations in Best disease and four different mutations in AVMD. Two of the mutations found in the AVMD patients were also seen in Best disease suggesting a considerable overlap in the aetiology of these two disorders. There were no mutations found in the AMD group. In addition, four frequent intragenic polymorphisms did not reveal allelic association of the VMD2 locus with AMD. These data exclude a direct role of VMD2 in the predisposition to AMD.

[Ophthalmological rehabilitation - experience at the University Eye Hospital Heidelberg]. / Ophthalmologische Rehabilitation. Erfahrungen an der Heidelberger Universitäts-Augenklinik.

BACKGROUND: The rehabilitation of low vision patients is of increasing importance since the number of these patients has grown rapidly. We wanted to evaluate the actual spectrum of patients concerning age and diagnoses and the appropriate low vision aids (LVA) in 1 year. METHODS: The records of the patients seen in our low-vision unit in 1996 were retrospectively evaluated. We correlated visual function, ophthalmological diagnoses and age to the magnification needed for rehabilitation and the use or prescribed LVAs. RESULTS: There was a nearly homogeneous distribution concerning age with a range from 0 to 99 years. Most patients presented with age-related macular degeneration (25.6 %) while 10 % each had retinitis pigmentosa and optic atrophy. Simple low vision aids such as high plus reading additions (29 %) and magnifiers (18.5 %) were prescribed in the majority of patients. However, closed-circuit TV (CCTV) systems were necessary in 25 %. CONCLUSIONS: Rehabilitation of low vision patients is often possible with simple LVAs. This is especially true for patients suffering from age-related macular degeneration. Since there is a tremendous-amount of different diseases, adequate diagnostic and individual counseling is of major importance.

The 2588G-->C mutation in the ABCR gene is a mild frequent founder mutation in the Western European population and allows the classification of ABCR mutations in patients with Stargardt disease.

In 40 western European patients with Stargardt disease (STGD), we found 19 novel mutations in the retina-specific ATP-binding cassette transporter (ABCR) gene, illustrating STGD's high allelic heterogeneity. One mutation, 2588G-->C, identified in 15 (37.5%) patients, shows linkage disequilibrium with a rare polymorphism (2828G-->A) in exon 19, suggesting a founder effect. The guanine at position 2588 is part of the 3' splice site of exon 17. Analysis of the lymphoblastoid cell mRNA of two STGD patients with the 2588G-->C mutation shows that the resulting mutant ABCR proteins either lack Gly863 or contain the missense mutation Gly863Ala. We hypothesize that the 2588G-->C alteration is a mild mutation that causes STGD only in combination with a severe ABCR mutation. This is supported in that the accompanying ABCR mutations in at least five of eight STGD patients are null (severe) and that a combination of two mild mutations has not been observed among 68 STGD patients. The 2588G-->C mutation is present in 1 of every 35 western Europeans, a rate higher than that of the most frequent severe autosomal recessive mutation, the cystic fibrosis conductance regulator gene mutation DeltaPhe508. Given an STGD incidence of 1/10,000, homozygosity for the 2588G-->C mutation or compound heterozygosity for this and other mild ABCR mutations probably does not result in an STGD phenotype.

Macular function testing in a German pedigree with North Carolina macular dystrophy.

BACKGROUND: Our purpose was to investigate central visual function in North Carolina macular dystrophy (MCDR1). A German family with genetically proven MCDR1 was followed for more than 20 years. METHODS: In addition to routine clinical examinations, static and kinetic fundus perimetry was performed with the scanning laser ophthalmoscope. The center of fixation was determined. RESULTS: Visual acuity was 0.6 or better in all but one eye of seven members of this family and did not markedly change during follow-up. Fundus examination confirmed that the fixation was at the nasal edge of the central scar in five affected eyes with reduced stability of fixation. One eye had a prominent gliotic membrane, and fixation was within this area. CONCLUSIONS: Patients had nearly normal visual acuity even though they presented with deep central scotomas and a shift of the center of fixation away from the fovea. Because MCDR1 has good long-term functional prognosis, there might be an early transdifferentiation of the new locus of fixation.

Ten novel mutations found in Aniridia.

Aniridia (AN) is a sight-threatening congenital ocular disorder characterized by iris hypoplasia, corneal pannus, foveal and optic nerve hypoplasia, cataract formation, and glaucoma. In two-thirds of the patients, AN is inherited in an autosomal dominant fashion with almost complete penetrance but variable expression. The remaining cases are sporadic. Aniridia has been shown to be associated with mutations in the PAX6 gene, located on chromosome 11p13, telomeric to the Wilms' tumor predisposition gene (WT1). This paper describes 14 mutations in the PAX6 gene in patients with AN. Among these 14 mutations, 10 have been unpublished until now. They result most probably in haploinsufficiency and consequently in a reduced protein level of functional PAX6 protein. The mutations reported here are scattered all over the gene, including the paired-box, the glycine-rich region, the homeobox, and the proline-serine-threonine (PST)-rich region.

Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt's disease gene ABCR.

Ophthalmological and molecular genetic studies were performed in a consanguineous family with individuals showing either retinitis pigmentosa (RP) or cone-rod dystrophy (CRD). Assuming pseudodominant (recessive) inheritance of allelic defects, linkage analysis positioned the causal gene at 1p21-p13 (lod score 4.22), a genomic segment known to harbor the ABCR gene involved in Stargardt's disease (STGD) and age-related macular degeneration (AMD). We completed the exon-intron structure of the ABCR gene and detected a severe homozygous 5[prime] splice site mutation, IVS30+1G->T, in the four RP patients. The five CRD patients in this family are compound heterozygotes for the IVS30+1G->T mutation and a 5[prime] splice site mutation in intron 40 (IVS40+5G->A). Both splice site mutations were found heterozygously in two unrelated STGD patients, but not in 100 control individuals. In these patients the second mutation was either a missense mutation or unknown. Since thus far no STGD patients have been reported to carry two ABCR null alleles and taking into account that the RP phenotype is more severe than the STGD phenotype, we hypothesize that the intron 30 splice site mutation represents a true null allele. Since the intron 30 mutation is found heterozygously in the CRD patients, the IVS40+5G->A mutation probably renders the exon 40 5[prime] splice site partially functional. These results show that mutations in the ABCR gene not only result in STGD and AMD, but can also cause autosomal recessive RP and CRD. Since the heterozygote frequency for ABCR mutations is estimated at 0.02, mutations in ABCR might be an important cause of autosomal recessive and sporadic forms of RP and CRD.

[Image flicker frequency of television reading aids. Effect on reading comfort for visually handicapped patients]. / Bildwiederholfrequenz von Bildschirmlesegeräten. Einfluss auf die Lesefähigkeit von Sehbehinderten.

PURPOSE: To compare reading speed and reading comfort between closed-circuit television systems (CCTVs) with different image refresh rates. METHODS: Reading speed was measured with three CCTVs that only differed in repeat frequency (50, 60 and 70 Hz) in 21 patients with age-related macular degeneration and 10 controls. We compared reading speed measured in syllables per minute of 16 different reading templates with about 500 syllables each. RESULTS: Reading speed was equal with all CCTVs. Eighteen of 21 patients identified and disliked 50 Hz CCTVs because the image quality was worse. An image quality of 70 HZ enabled patients to use positive contrast with the best reading speed. CONCLUSIONS: Although reading speed does not improve with increasing frequency, flickering of 50 Hz CCTVs is critical for low-vision patients. The preference of low-vision patients for negative contrast image is more likely due to flickering with a lower repeat rate and 70 Hz CCTVs may allow more comfortable reading in positive contrast.

Complete exon-intron structure of the retina-specific ATP binding transporter gene (ABCR) allows the identification of novel mutations underlying Stargardt disease.

Stargardt disease, an autosomal recessive macular dystrophy of childhood, leading to severe visual impairment, is caused by mutations in the retina-specific ATP binding transporter gene (ABCR). Previously, the ABCR cDNA and part of the exon-intron structure were described. We have determined the complete ABCR exon-intron structure by exon-exon PCR. The ABCR gene encompasses 50 exons, 29 of which are first described here with their corresponding intron-exon boundaries. The discovery of a splicing mutation (571: 2A-->G) and missense mutations in the newly identified exons (R18W, R212C) gives additional support to the broad allelic heterogeneity of Stargardt disease.

[Molecular genetic study of the PAX6 gene in aniridia patients]. / Molekulargenetische Untersuchung des PAX6-Gens bei Aniridie-Patienten.

INTRODUCTION: Aniridia represents a congenital ocular disorder with partial or complete iris hypoplasia. The disorder is associated with poor vision, glaucoma, corneal and lenticular opacities, ectopia lentis due to abnormal zonula fibers, as well as optic nerve and macular abnormalities. Aniridia may present as either hereditary or sporadic cases. Some of the sporadic cases develop Wilms' tumor, frequently as part of the WAGR syndrome (Wilms' tumor, aniridia, genitourinary abnormalities and mental retardation). PAX6, a candidate gene located on chromosome 11p13, is often mutated in aniridia patients. The gene encodes a transcription regulatory protein. METHOD: Analysis of the PAX6 gene was done using PCR (polymerase chain reaction), SSCP (single strand conformation polymorphism) and DNA sequencing. RESULTS: In 13 of 20 aniridia patients a PAX6 gene mutation was found. CONCLUSION: The mutations result in a gene product with reduced function or a reduced PAX6 protein level. Molecular analysis of aniridia is also a valuable diagnostic tool for Wilms' tumor risk evaluation, as patients with proven PAX6 mutations--in contrast to cases with large deletions of the 11p13 region--are at no increased risk to develop Wilms' tumor.

[Fixation behavior in Stargardt disease. Fundus-controlled studies]. / Fixationsverhalten bei Morbus Stargardt. Funduskontrollierte Untersuchungen.

UNLABELLED: Patients with Stargardt's disease often show a significantly reduced ability to read despite fairly good visual acuity. We evaluated whether fundus perimetry with simultaneous observation of the point of fixation can help to explain these difficulties. METHODS: A total of 40 eyes in 21 patients with Stargardt's disease were examined by means of automatic fundus threshold perimetry and special fixation tasks using a scanning laser ophthalmoscope (SLO). RESULTS: During fundus perimetry 19 eyes showed a movement of the mean fixation point towards the top, and five to the right of the central scotoma. At the same time, the variation around the mean fixation point was orientated vertically. We observed an alternation between two different points of fixation in another eight eyes. While one fixation point was usually located in the center inside an area of reduced light sensitivity, the second new locus of fixation was at the top of the scotoma (six of eight eyes). Patients tried to fix small targets inside the scotomatous area. CONCLUSION: Our results demonstrate that patients with Stargardt's disease exhibit a typical pattern of fixation. The development of eccentric fixation occurs in three steps: The initial phase is characterized by central fixation with decreased stability. In the intermediate phase, we observed alternation between central and eccentric fixation. Finally, patients develop a constant eccentric fixation. These results may explain the difficulties in reading which many Stargardt's patients experience and the problems in prescribing corrective devices for these patients.

[Complicated cataracts in various forms of retinitis pigmentosa. Type and incidence]. / Cataracta complicata bei verschiedenen Formen der Retinitis pigmentosa. Art und Häufigkeit.

PURPOSE: To study the incidence and types of cataract in retinitis pigmentosa (RP) and their variations among different forms of RP. PATIENTS AND METHODS: This analysis was based on data from 473 patients with RP (autosomal dominant, n = 87; autosomal recessive, n = 79; x chromosomal recessive, n = 23; simplex RP, n = 215; Usher's syndrome n = 80; M. Refsum and others, n = 9) that were retrieved from the literature and patient charts in our clinic. RESULTS: Posterior subcapsular cataract (PSC) developed with the following frequencies for the different genetic types of RP: autosomal dominant, 45.3%; autosomal recessive, 44.0%; x chromosomal recessive, 40.7%; simplex RP, 46.1%; Usher's syndrome, 52.9%. PSC was the only type of lens opacity in patients with Usher's syndrome and autosomal recessive RP.PSC development correlated with early onset of RP symptoms. Nuclear cataracts showed a statistically significant higher frequency in patients with simplex RP (14.8%) than in other genetic types (0-5.9%) (P < 0.01). In addition, nuclear cataracts developed in simplex RP at a significantly later age (69.6 +/- 12.4 years) than PSC (44.4 +/- 12.3 years) (P < 0.001). Patients with cataracts showed significantly worse visual fields than patients with clear lenses (P = 0.00067). CONCLUSIONS: The typical RP cataract (PSC) was found in similar frequencies among all genetic types of RP.PSC was the only type of lens opacity in patients with Usher's syndrome and autosomal recessive RP. Nuclear cataracts developed on average 20 years later than PSC and had their highest incidence in patients with simplex RP. Patients with cataracts showed significantly worse visual field results, indicating a more pronounced retinal pathology.

[Use of a new optoelectronic vision aid for highly visually handicapped patients]. / Anwendungen einer neuen optoelektronischen Sehhilfe für hochgradig Sehbehinderte (LVES).

UNLABELLED: A new low vision aid (LVA)-the Low Vision Enhancement System or LVES, which were as developed at the Johns Hopkins University in Baltimore, is now commercially available. This instrument allows a magnification up to 10 times with control of contrast and luminance while the field of view is very large: 60 x 40 degrees. We present first results concerning LVES in comparison to conventional LVAs. PATIENTS AND METHODS: 60 consecutive patients suffering from macular dystrophy, macular degeneration, optic atrophy, tapetoretinal degeneration, or diabetic retinopathy were included in this study. We compared visual acuity with glasses, with telescope and using LVES. Furthermore we compared contrast acuity by the use of the Pelli-Robson-charts as well as the subjective impression of the patients. RESULTS: Improvement of visual acuity with LVES compared to correction with glasses was 8 log steps on average and up to 3 steps as compared to the use of telescopes. More important is the improvement of contrast sensitivity (0-16 steps) and the reduced glare. Despite the subjective improvement of visual acuity and contrast sensitivity the majority of patients could not imagine to use LVES regularly. A significant improvement as compared to conventional low vision aids is possible for special applications such as office work, recognition of faces or images or for looking at a blackboard. CONCLUSION: In addition to traditional LVAs, the Low Vision Enhancement System opens up possibilities for a very small group of patients. Especially patients suffering from macular dystrophy or Lebers optic atrophy may benefit from this new system. The most important advantage of LVES is the improvement of contrast sensitivity and the significantly decreased glare sensitivity. Additionally the near working distance is changeable. The variable magnification allows an easier fitting to various tasks. Prior to the prescription of LVES a detailed and time consuming testing is necessary.

An ancestral core haplotype defines the critical region harbouring the North Carolina macular dystrophy gene (MCDR1).

Autosomal dominant North Carolina macular dystrophy (NCMD) or central areolar pigment epithelial dystrophy (CAPED) is an allelic disorder that maps to an approximately 7.2 cM interval between DNA markers at D6S424 and D6S1671 on 6q14-q16.2. The further refinement of the disease locus has been hindered by the lack of additional recombination events involving the critical region. In this study, we have identified three multigeneration families of German descent who express the NCMD phenotype. Genotyping was carried out with a series of markers spanning approximately 53 cM around the NCMD locus, MCDR1. Genetic linkage between the markers and the disease phenotype in each of the families could be shown. Disease associated haplotypes were constructed and provide evidence for an ancestral founder for the German NCMD families. This haplotype analysis suggests that a 4.0 cM interval flanked by markers at D6S249 and D6S475 harbours the gene causing NCMD, facilitating further positional cloning approaches.

Fundus-controlled examination of reading in eyes with macular pathology.

The ability to read is an important parameter for the optical rehabilitation of visually handicapped patients. For the choice of the best therapy, more detailed knowledge of the physiology of reading is required. We evaluated reading velocity as well as the number of saccades in and against the direction of reading for reading plates with different character sizes (10 steps from a letter height of 3-0.25 degrees) using the scanning laser ophthalmoscope in 20 healthy eyes and 30 eyes with central and paracentral scotomas. The number of characters read during each fixation increased with decreasing size of characters from 3.2 to 4.4 in normals. However, the reading velocity decreased from 14 to 11 digits/s when digits became very small. In patients' eyes the greatest reading velocity was reached at 6.1 digits/s for a 1 degree size, and the maximal number of digits read during one rest phase was 3.2 for a 0.75 degree size. In patients we observed a high number of saccades against the reading direction and different loci of fixation. Fundus-controlled examination allows for new insights into the physiology and pathophysiology of reading. Loss of the central visual field leads to an increase in the number of saccades because the number of digits perceived during each fixation decreases. The high number of regressions may be caused by the typical shift of the center of fixation following paracentral scotoma. Saccades directed toward the scotoma have to be corrected due to failure of exact positioning.