Erratum: Motion-Acuity Test for Visual Field Acuity Measurement with Motion-Defined Shapes.

This corrects the article 10.3791/66272.

Motion-Acuity Test for Visual Field Acuity Measurement with Motion-Defined Shapes.

The standard visual acuity measurements rely on stationary stimuli, either letters (Snellen charts), vertical lines (vernier acuity) or grating charts, processed by those regions of the visual system most sensitive to the stationary stimulation, receiving visual input from the central part of the visual field. Here, an acuity measurement is proposed based on discrimination of simple shapes, that are defined by motion of the dots in the random dot kinematograms (RDK) processed by visual regions sensitive to motion stimulation and receiving input also from the peripheral visual field. In the motion-acuity test, participants are asked to distinguish between a circle and an ellipse, with matching surfaces, built from RDKs, and separated from the background RDK either by coherence, direction, or velocity of dots. The acuity measurement is based on ellipse detection, which with every correct response becomes more circular until reaching the acuity threshold. The motion-acuity test can be presented in negative contrast (black dots on white background) or in positive contrast (white dots on black background). The motion defined shapes are located centrally within 8 visual degrees and are surrounded by RDK background. To test the influence of visual peripheries on centrally measured acuity, a mechanical narrowing of the visual field to 10 degrees is proposed, using opaque goggles with centrally located holes. This easy and replicable narrowing system is suitable for MRI protocols, allowing further investigations of the functions of the peripheral visual input. Here, a simple measurement of shape and motion perception simultaneously is proposed. This straightforward test assesses vision impairments depending on the central and peripheral visual field inputs. The proposed motion-acuity test advances the capability of standard tests to reveal spare or even strengthened vision functions in patients with injured visual system, that until now remained undetected.

Motion-Based Acuity Task: Full Visual Field Measurement of Shape and Motion Perception.

Purpose: Damage of retinal representation of the visual field affects its local features and the spared, unaffected parts. Measurements of visual deficiencies in ophthalmological patients are separated for central (shape) or peripheral (motion and space perception) properties, and acuity tasks rely on stationary stimuli. We explored the benefit of measuring shape and motion perception simultaneously using a new motion-based acuity task. Methods: Eight healthy control subjects, three patients with retinitis pigmentosa (RP; tunnel vision), and 2 patients with Stargardt disease (STGD) juvenile macular degeneration were included. To model the peripheral loss, we narrowed the visual field in controls to 10 degrees. Negative and positive contrast of motion signals were tested in random-dot kinematograms (RDKs), where shapes were separated from the background by the motion of dots based on coherence, direction, or velocity. The task was to distinguish a circle from an ellipse. The difficulty of the task increased as ellipse became more circular until reaching the acuity limit. Results: High velocity, negative contrast was more difficult for all, and for patients with STGD, it was too difficult to participate. A slower velocity improved acuity for all participants. Conclusions: Proposed acuity testing not only allows for the full assessment of vision but also advances the capability of standard testing with the potential to detect spare visual functions. Translational Relevance: The motion-based acuity task might be a practical tool for assessing vision loss and revealing undetected, undamaged, or strengthened properties of the injured visual system by standard testing, as suggested here for two patients with STGD and three patients with RP.

Complex Phenotypic Presentation of Syndromic Hearing Loss Deciphered as Three Separate Clinical Entities: How Genetic Testing Guides Final Diagnosis.

BACKGROUND: Genetically determined prelingual hearing loss (HL) may occur in an isolated or syndromic form. OBJECTIVE: The aim of the study was to unravel the genetic cause of medical problems in a 21-year-old woman, whose phenotypic presentation extended beyond Stickler syndrome and included enlarged vestibular aqueduct (EVA) and persistent microhematuria. METHODS AND RESULTS: After sequencing of clinical exome, a known de novo COL2A1 pathogenic variant (c.1833+1G>A, p.?) causative for Stickler syndrome and one paternally inherited pathogenic change in COL4A5 (c.1871G>A, p.Gly624Asp) causative for X-linked Alport syndrome were found. No pathogenic variants, including those within the SLC26A4 5' region (Caucasian EVA haplotype), explaining the development of EVA, were identified. CONCLUSIONS: The study reveals a multilocus genomic variation in one individual and provides a molecular diagnosis of two HL syndromes that co-occur in the proband independent of each other. For the third entity, EVA, no etiological factor was identified. Our data emphasize the relevance of detailed clinical phenotyping for accurate genotype interpretation. Focus on broadening the phenotypic spectrum of known genetic syndromes may actually obscure patients with multiple molecular diagnoses.

Molecular Analysis of the ABCA4 Gene Mutations in Patients with Stargardt Disease Using Human Hair Follicles.

ABCA4 gene mutations are the cause of a spectrum of ABCA4 retinopathies, and the most common juvenile macular degeneration is called Stargardt disease. ABCA4 has previously been observed almost exclusively in the retina. Therefore, studying the functional consequences of ABCA4 variants has required advanced molecular analysis techniques. The aim of the present study was to evaluate whether human hair follicles may be used for molecular analysis of the ABCA4 gene splice-site variants in patients with ABCA4 retinopathies. We assessed ABCA4 expression in hair follicles and skin at mRNA and protein levels by means of real-time PCR and Western blot analyses, respectively. We performed cDNA sequencing to reveal the presence of full-length ABCA4 transcripts and analyzed ABCA4 transcripts from three patients with Stargardt disease carrying different splice-site ABCA4 variants: c.5312+1G>A, c.5312+2T>G and c.5836-3C>A. cDNA analysis revealed that c.5312+1G>A, c.5312+2T>G variants led to the skipping of exon 37, and the c.5836-3C>A variant resulted in the insertion of 30 nucleotides into the transcript. Our results strongly argue for the use of hair follicles as a model for the molecular analysis of the pathogenicity of ABCA4 variants in patients with ABCA4 retinopathies.

Processing of OPA1 with a novel N-terminal mutation in patients with autosomal dominant optic atrophy: Escape from nonsense-mediated decay.

Autosomal Dominant Optic Atrophy (ADOA) is the most common dominantly inherited optic neuropathy. In the majority of patients it is caused by OPA1 mutations and those predicted to introduce a premature termination codon (PTC) are frequently detected. Transcripts containing PTC may be degraded by nonsense-mediated mRNA decay (NMD), however very little is known about an effect of OPA1 mutations on NMD activation. Here, using a combination of linkage analysis and DNA sequencing, we have identified a novel c.91C>T OPA1 mutation with a putative premature stop codon (Q31*), which segregated with ADOA in two Polish families. At the mRNA level we found no changes in the amount of OPA1 transcript among mutation carriers vs. non-carriers. Specific allele quantification revealed a considerable level of the OPA1 mutant transcript. Our study identifies a novel pathogenic OPA1 mutation and shows that it is located in the transcript region not prone for NMD activation. The data emphasizes the importance of analyzing how mutated genes are being processed in the cell. This gives an insight into the molecular mechanism of a genetic disease and promotes development of innovative therapeutic approaches.

Is it appropriate to perform anterior segment reconstruction in amblyopic eye following penetrating trauma in childhood?

We present a case of diagnostic and surgical management in an amblyopic eye following penetrating trauma in childhood. The 75-year-old female patient experienced the trauma at the age of 4. The eye was amblyopic, but after thorough investigations (ultrasonography, ultrabiomicroscopy, visual evoked potentials) the eye underwent anterior segment reconstruction. Visual evoked potentials allowed us to assess optic nerve function, while ultrabiomicroscopy allowed us to plan the surgical procedure. Although we observed quite a small visual acuity improvement, the subjective improvement reported by the patient was fairly significant (NEI VFQ-25 questionnaire). The cosmetic effect of the black pupil was also important.

ORF15 exon of the RPGR gene in retinitis pigmentosa ­ technically difficult, diagnostically important. / Trudny technicznie, wazny diagnostycznie ­ ekson ORF15 genu RPGR w zwyrodnieniu barwnikowym siatkówki.

The aim of the study was to identify the genetic background of retinitis pigmentosa in a Polish family with previously excluded involvement of the majority of known genes for this disease, except for the ORF15 exon in the RPGR gene (Xp21.1). ORF15 is a highly repetitive, purine-rich DNA region with a number of different polymorphic variants and thus difficult to study. Genomic DNA was isolated from peripheral blood of the family members (n = 9). ORF15 exon was amplified in a long-range polymerase chain reaction and sequenced using the next generation method. Presence of the identified variant was confirmed by direct Sanger sequencing of the amplicon encompassing the mutation. The NM_001034853:c.2899delG (p.E967Kfs*122) mutation was detected in the ORF15 region. It completely segregated with the disease in the studied family. The identified alteration is pathogenic and has already been found to cause retinitis pigmentosa. It is estimated that more than a half of RPGR mutations are located in the ORF15 region. In families with a suspected X-linked inheritance of retinitis pigmentosa and in males with a negative family history of the disease, genetic tests should begin with an analysis of the ORF15.

Next-generation sequencing of ABCA4: High frequency of complex alleles and novel mutations in patients with retinal dystrophies from Central Europe.

Variation in the ABCA4 locus has emerged as the most prevalent cause of monogenic retinal diseases. The study aimed to discover causative ABCA4 mutations in a large but not previously investigated cohort with ABCA4-related diseases originating from Central Europe and to refine the genetic relevance of all identified variants based on population evidence. Comprehensive clinical studies were performed to identify patients with Stargardt disease (STGD, n = 76) and cone-rod dystrophy (CRD, n = 16). Next-generation sequencing targeting ABCA4 was applied for a widespread screening of the gene. The results were analyzed in the context of exome data from a corresponding population (n = 594) and other large genomic databases. Our data disprove the pathogenic status of p.V552I and provide more evidence against a causal role of four further ABCA4 variants as drivers of the phenotype under a recessive paradigm. The study identifies 12 novel potentially pathogenic mutations (four of them recurrent) and a novel complex allele p.[(R152*; V2050L)]. In one third (31/92) of our cohort we detected the p.[(L541P; A1038V)] complex allele, which represents an unusually high level of genetic homogeneity for ABCA4-related diseases. Causative ABCA4 mutations account for 79% of STGD and 31% of CRD cases. A combination of p.[(L541P; A1038V)] and/or a truncating ABCA4 mutation always resulted in an early disease onset. Identification of ABCA4 retinopathies provides a specific molecular diagnosis and justifies a prompt introduction of simple precautions that may slow disease progression. The comprehensive, population-specific study expands our knowledge on the genetic landscape of retinal diseases.

Optical coherence tomography and electrophysiology of retinal and visual pathways in Wilson's disease.

We evaluated correlations between positive findings of changes on brain magnetic resonance imaging (MRI) and selected morphological and electrophysiological parameters of the retinal and visual systems in Wilson's disease. Fifty-eight Wilson's disease symptomatic patients were divided according to whether they displayed brain changes on MRI (positive, n = 39; negative, n = 19). All participants and healthy control group (n = 30), underwent retinal optical coherence tomography to assess the thickness of macula and the total retinal nerve fiber layer. Visual evoked potentials were measured and electroretinography was performed. Macular and retinal nerve fibers were thinner in participants with changes on MRI than in participants without changes. Electrophysiological parameters were markedly different in the MRI positive group compared with the negative group and 30 healthy controls; however, some abnormalities were evident in cases without visible brain pathology. Morphological and electrophysiological changes of retinal and visual pathways are associated with MRI visualized brain injury in Wilson's disease and may be useful for detecting the degree of neurodegeneration.

Electrophysiological testing as a method of cone-rod and cone dystrophy diagnoses and prediction of disease progression.

PURPOSE: To determine the characteristics of patients with cone (CD) and cone-rod dystrophies (CRD) and to evaluate the changes in flash electroretinograms in both groups. METHODS: The retrospective study involved 48 patients-34 with CRD and 14 with CD. The patients underwent full ophthalmological examination, including Goldmann perimetry and full-field flash electroretinogram (FERG) within the initial examination. These examinations were then repeated seven, or more, years later. The longest follow-up period was 10 years, with the mean at 8.2 years. During both examinations, we assessed the amplitudes of the b wave in the scotopic ERG test 0.01 (which reflects rod response), the maximal scotopic ERG test 3.0 (which reflects cone and rod response) and the photopic 3.0 ERG test (which reflects cone response). The results were then compared against normal values. RESULTS: The progression over time of ERG b wave amplitudes in the scotopic ERG 0.01, maximal scotopic ERG 3.0 and photopic ERG tests was assessed. There were significant differences in rod, maximal and cone responses, between CD and CRD patients. While rod responses were markedly decreased in CRD patients during their initial examination, the decrease in the rod function in both CD and CRD patients was similar in their follow-up examination (p = 0.2398). Moreover, during initial examination, maximal responses were less common amongst CRD patients, over those with CD. Following the observation period, patients suffering from CRD exhibited a significant decrease in both maximal (p = 0.0125) and cone (p = 0.0046) responses. CONCLUSION: The clinical course of CRD and CD may vary; however, the latter appears to have a more favourable course than former. Although, at initial examination, the cone function was more diminished in CD patients, the final examinations reveal a more significant drop for CRD patients. Consequently, a differential diagnosis is essential for treating patients and forecasting their disease progression.

[Not only optic neuropathy: new molecular and clinical aspects of OPA1 gene mutations]. / Nie tylko neuropatia wzrokowa: nowe aspekty molekularne i kliniczne mutacji w genie OPA1.

Autosomal dominant optic nerve atrophy is the most frequent dominantly inherited optic neuropathy. The main causesof the disease are OPA1 gene mutations, which are detected in about 60% of patients. Encoded by the nuclear genome the OPA1 protein plays an important role in a wide variety of processes crucial to the proper functioning of mitochondria, the role of OPAl in many of them has been discovered recently. A detailed study of patients with mutations in the OPA1 gene has shown that about 20% of them present symptoms of a multiple system disease, which may include hearing loss, progressive external ophthalmoplegia, ataxia, myopathy, peripheral neuropathy, spastic paraparesis and multiple sclerosis-like illness. This clinical manifestation is difficult to differentiate from other neurodegenerative diseases, that is why genetic testing is very important in order to determine the molecular basis of the disease in these patients.

Evidence against RAB40AL being the locus for Martin-Probst X-linked deafness-intellectual disability syndrome.

RAB40AL has been reported as the locus for Martin-Probst syndrome (MPS), an X-linked deafness-intellectual disability syndrome. The report was based on segregation of a missense change p.D59G with the disease in a single family and in vitro localization studies. We found the p.D59G variant by whole-exome sequencing in two patients; however, the diagnosis of MPS was excluded in both cases. Furthermore, screening of control DNA samples (n = 810) from a general Polish population, using allele-specific PCR and direct DNA sequencing for verification, identified p.D59G in 8/405 males and 12/405 females. High prevalence of the p.D59G variant (2.47%) is typical for a common genetic variation observed in asymptomatic individuals. Our data question the role of RAB40AL mutation as a disease-causing change and the involvement of RAB40AL in MPS. Considering an increasing use of next-generation sequencing in the clinical setting, our finding is of practical diagnostic importance.

X-linked retinoschisis--clinical manifestation, genetic and electrophysiological analysis of three generations with p.Arg197Cys mutation of RS1 gene.

The aim of the study is to present an atypical case of late-onset X-linked retinoschisis. We present a case of a 37 year-old male patient with a few months' history of visual impairment. A clinical exam with optical coherence tomography and flash electroretinography (flash-ERG) was performed and the patient was diagnosed with X-linked retinoschisis. Genetic testing of the patient's family confirmed the disease and p.Arg197Cys mutation of RS1 gene was identified. In conclusion, optical coherence tomography and flash electroretinography enabled a proper diagnosis of X-linked retinoschisis in a patient with symptoms manifesting in the fourth decade of life. Genetic testing revealed male sufferers and female carriers among his family members.

Visual evoked potentials in early diagnosis of demyelinating diseases--a case report of Devic's disease.

BACKGROUND: Devic's disease, also known as neuromyelinitis optica (NMO), is a severe, rare demyelinating disorder, previously considered to be a form of multiple sclerosis (MS). The aim of this study was to present the case report of 21-year-old woman with a very early diagnosis of Devic's disease, established following electrophysiological testing. CASE REPORT: A 21-year-old woman was referred to Warsaw Medical University, Department of Ophthalmology, with subjective visual impairment. The patient underwent a full clinical examination, colour vision and Goldmann visual field testing, fluorescein angiography, OCT, multifocal ERG, and visual evoked potentials (VEPs). CONCLUSIONS: Visual evoked potentials are a very useful diagnostic tool in optic nerve neuropathies. In our patient, the electrophysiological testing allowed us to establish a proper diagnosis very early, before typical clinical signs of Devic's disease.

A clinical case study of a Wolfram syndrome-affected family: pattern-reversal visual evoked potentials and electroretinography analysis.

Wolfram syndrome (WFS), or DIDMOAD, is a rare (1/100 000 to 1/770 000), progressive neurodegenerative disorder. In its early stages, it is characterized by insulin-dependent diabetes mellitus, optic atrophy and loss of sensorineural hearing-this is followed by diabetes insipidus, progressive neurological abnormalities and other endocrine abnormalities, which occur in later years. The aim of this study was to report on the clinical and electrophysiological findings from a family with the WFS1 mutation. The five family members were subjected to a complete ophthalmic examination, which included a flash full-field electroretinogram and pattern-reversal visual evoked potentials (PVEPs) performed according to ISCEV standards. Optic atrophy was confirmed in two homozygotic patients, where P100 latencies were significantly delayed-up to 146 ms in PVEP. P100 latencies were normal in the three heterozygotic patients we examined. Curve morphology abnormalities were observed in all five patients we examined. No literature describing the morphology of PVEP in Wolfram syndrome patients was found. In flash electroretinography, scotopic and photopic responses appeared in normal morphology and value. Diabetic retinopathy was not observed in the diabetes mellitus patients.

The impact of capsulorhexis diameter, localization and shape on posterior capsule opacification.

BACKGROUND: The aim of this study was to evaluate the impact of capsulorhexis diameter, localization and shape on posterior capsule opacification (PCO) development after cataract extraction with phacoemulsification. MATERIAL/METHODS: We retrospectively analyzed of 297 patients who underwent phacoemulsification and AcrySof SA60AT implantation. In a first group of 97 patients, 53 received small capsulorhexis (3.9 to 4.9 mm in diameter) and 44 patients received large capsulorhexis (5.0 to 5.9 mm in diameter). Another group of 99 patients was split into subgroups--66 patients whose capsulorhexis were centrally located and 33 patients whose capsulorhexis were paracentral. A third group of 101 patients was split into subgroups--a subgroup of 59 patients were classified as having a regularly rimmed capsulorhexis and a subgroup of 42 patients as having an irregularly rimmed capsulorhexis. At 6 months follow-up, PCO was classified as none, mild, moderate, or severe, depending on the number of quadrants involved. RESULTS: 86.79% of the patients with a small capsulorhexis had no or mild PCO (p<0.001), whereas, 68.18% of the patients with a large capsulorhexis experienced moderate or severe PCO; 89.4% of the patients with a central capsulorhexis had no or mild PCO (p<0.001), whereas, 75.75% of the patients with a paracentral capsulorhexis had moderate or severe PCO; 86.44% of the patients with a regularly rimmed anterior capsulorhexis had no or mild PCO (p<0.001); and 69.04% of the patients with an irregular capsulorhexis rim had moderate or severe PCO. CONCLUSIONS: A small capsulorhexis diameter, its central localization and regular shape result in less PCO following phacoemulsification.

A retrospective analysis of the intraocular lens power calculation in cases of sulcus fixation.

PURPOSE: To evaluate the refractive results in patients with intraocular lenses fixated in the sulcus of posterior chamber. Sulcus fixation causes a more anterior position of IOL than had been intended during the preoperative power calculation. A lack of correction of the IOL's power results in a myopic shift. MATERIAL AND METHODS: 27 patients (27 eyes) who underwent cataract surgery by phacoemulsification and foldable IOL MA60BM sulcus fixation due to a posterior capsule rupture at the Department of Ophthalmology, Medical University of Warsaw. The position of the IOL was confirmed by ultrabiomicroscopy. The study included patients with axial lengths ranging from 22 to 25 mm. Patients who suffered from a corneal astigmatism of > 1,00 Dcyl prior to the surgery were excluded from the study. The study also excluded patients with vitreous loss as this causes the anterior chamber to become deeper after vitrectomy, and consequently the IOL might sit in a more posterior position. The difference between the predicted and the postoperative refraction was evaluated. RESULTS: The mean visual acuity was significantly better after cataract surgery. The best corrected visual acuity (BCVA) was 1.0, which occurred in 19 cases (70%). The myopic shift, which was assessed as a mean difference between the predicted and the postoperative refraction after sulcus fixation, was 1.25 D. CONCLUSIONS: In order to avoid a myopic shift in the case of sulcus fixation, the IOL power calculation should be adjusted accordingly. The authors recommend that the IOL power should be reduced by approximately 1.25 to 1.50 D in emetropic eyes.

The complications during phacoemulsification in patients with posterior polar cataract.

PURPOSE: The aim of the study was to evaluate the intraoperative complications during phacoemulsification of a posterior polar cataract, especially the risk of posterior capsule rupture. MATERIAL AND METHODS: The retrospective evaluation of complications during phacoemulsification of a posterior polar cataract in patients in the Department of Ophthalmology, Medical University of Warsaw from January 2001 to June 2007. The surgical procedures, as well as the implanted IOL type and intraoperative and postoperative complications were evaluated in every case in 2 years' observations. Best-corrected visual acuity before and 3 months after surgery was evaluated using the standard Snellen chart. RESULTS: The study group consisted of 16 individuals, 6 women and 10 men in age 21-55 (mean 32.7). 22 eyes were operated on, all using the phacoemulsification method through corneal incision (10 individuals--1 eye, 6 individuals--both eyes). In all cases, phacoemulsification was performed using a hydrodissection free technique by corneal incision. A posterior capsule rupture was observed in 4 eyes (18%), localized in the central region and caused by changes in the capsula. The mean visual acuity was significantly better after cataract surgery. The best corrected visual acuity (BCVA) was 6/6 in 8 eyes (36%). A BCVA of less than 1.0 was caused by either amblyopia or nystagmus. CONCLUSIONS: Phacoemulsification in patients with posterior polar cataract is associated with a high risk of posterior capsule rupture and potential vitreous loss, which is why this procedure should be performed carefully by senior surgeons using an appropriate, hydrodissection free technique.

Late onset cone dystrophy.

Cone dystrophies are a hereditary, progressive and heterogeneous group of retinal diseases with cone system degeneration. They lead to reduced visual acuity, colour vision impairment and photophobia. Full-field electroretinogram (ERG) reveals severe cone function impairment, with normal rod responses or slightly depressed in advanced stages in some cases. The purpose of the study was to present a case of late onset cone dystrophy in 47-year-old male and the proper diagnostic procedure. A 47-year-old patient presented with progressive visual loss for several years and mild photophobia, which he observed recently. The patient underwent fundus photography, fluorescein angiography, colour vision testing, Goldmann visual field testing, full-field electroretinogram (ERG) and multifocal electroretinogram (mfERG). Symptoms and signs of late onset cone dystrophy may be unclear and establishing the proper diagnosis may be difficult in these cases. Patients may be misdiagnosed as having other diseases, especially in case of absence or subtle changes in the macula. The electrophysiological testing is essential in these cases, and ERG is the most useful clinical test in early and differential diagnosis of retinal dystrophies.