Color Vision Disturbances Research Articles

The presenting visual symptoms of optic chiasmal disease.

Recognising optic chiasmal disease early is important in order to avoid irreversible visual loss and the potential risk of mortality for patients. Yet, there is frequently a delay in the initial diagnosis. Whilst the signs of optic chiasmal disease, particularly the perimetric findings, are well documented in the recent literature, the symptoms have been less well reported. Whilst some patients with optic chiasmal disease will be asymptomatic, many will complain of visual symptoms including symptomatic field defects, problems with central vision, difficulty with near tasks, binocular visual disturbances, colour vision disturbances, photophobia, phosphenes, glare, and rarely, oscillopsia and visual hallucinations. Others may have headache or the severe and sudden visual symptoms associated with pituitary apoplexy. The visual symptoms may be vague or non-specific, even when there are significant bitemporal visual field defects. We aim in this review to describe the presenting visual symptoms of optic chiasmal disease, and to illustrate these with selected qualitative descriptions from the literature. Our hope is that this will aid clinicians in eliciting a careful history of the sometimes subtle symptoms that may be present.

Prototyp eines Bildschirmfarbtests

Purpose. The purpose of this study is to develop a new digital colour vision test. Material and Methods. Based on the principle of metamerism, a digital testing strategy was developed for efficient measurement of colour vision. Twentyfive subjects participated in the study, 21 of whom had normal colour vision and four of whom had a congenital colour vision disorder. Differences in colour vision were examined by monocular presentation of halfquadrants of different hues and degrees of saturation, and the algorithm calculated the colour vision defects that occurred based on the subjects’ responses. The following colour vision values were assigned from the data: a colour scale range of 2.76 – 7.18 for normal colour vision and greater than 7.18 for colour sense disorders. A second new colour scale assessed the type of colour vision disturbance: in the range of 0 – 0.3 were values for a deuteranomaly, in the range of 0.6 – 1.0 were values for a protanomaly, and a value of 1.0 corresponded to a tritanomaly. Results. The difference in colour vision between subjects with normal colour vision and those with a colour vision defect was confirmed (p < 0.001) by measuring the type and the extent of the colour vision disorder was determined. In the group of subjects with normal colour perception, a mean colour scale value of 3.41 ± 0.52 was determined. The extent of colour sense disturbance for the subjects with colour vision impairment was values of 7.18 – 14.33 according to the colour scale, indicating greater variability. Conclusion. The developed algorithm provided meaningful results regarding the colour perception of the test persons. It was possible to differentiate between normal colour vision and colour vision disorder could be shown. Furthermore, the variation between subjects with normal colour vision could be evaluated. Keywords. Colors, colour vision, colour sense disorders, colour test, software algorithm

Association of Tuberculosis in Patients with Chronic Myeloid Leukemia, a Treatment Proposal Based on Literature Review

Introduction: Chronic Myeloid leukemia (CML) is a chronic myeloproliferative neoplasm with an increased undifferentiated proliferation of granulocytic lineage of the white blood cells. It is an acquired disorder of the hematopoietic stem cells due to a cytogenetic aberration known as the Philadelphia chromosome. It occurs due to a phenomenon of a reciprocal translocation between chromosomes t(9,22) and results in BCR/ABL fusion gene. The product of this gene has tyrosine kinase property, which predominantly causes the disease. Tyrosine kinase inhibitors (TKI) are the mainstay of the treatment to achieve remission, while bone marrow transplant is the only proven cure. Tuberculosis (TB), both active and reactivation of latent TB, remains the most common infectious disease worldwide and leads to high mortality. Currently, one-fourth of the global population has been infected by Mycobacterium tuberculosis. The incidence of TB has been reportedly increasing in patients with cancer. It has been mostly found in association with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Recently, the incidence increased in patients with CML during treatment with Imatinib (IM) has also been reported in a retrospective cohort study in Taiwan by Lui C-J et. al. and few other published cases in literature. This might be due to impairment of the T lymphocytes signal transduction leading to increased host susceptibility to TB, hepatitis B, and varicella-zoster infection. TB treatment is mainly based on the susceptibility of the Mycobacterium Tuberculosis to the anti-TB medications. First-line therapy includes of four drugs, Isoniazid (INH), Rifampicin (RIF), Pyrazinamide (PZA), and Ethambutol (EMB). Anti TB drugs administration also needs close monitoring because of potential side effects. These include, but not limited to hepatoxicity, optic neuritis, impaired color vision, peripheral neuropathy, and gastrointestinal disturbances. Their occurrence necessitate discontinuation of the culprit drug from the regimen. Certain anti TB drugs are also known to disrupt bioavailability of other drugs metabolized in the liver when concomitantly administered by influencing the hepatic cytochrome P450 enzyme. This happens while using anti-TB medication to treat concomitant TB infection in CML patients on tyrosine kinase inhibitors therapy. Methods and critical analysis of the reviewed study articles: The authors reviewed the current literature focusing on all articles addressing TB infections and their diagnosis and management in patients with CML (PubMed and Google Scholar between 2000 and 2020). Our review aimed to provide the necessary data to improve clinical diagnosis and clarify the management strategy of this condition. Conclusion and treatment proposal: Throughout our review of multiple research articles, it has been realized that patients with CML and other hematological malignancies and solid tumors (e.g., non-Hodgkin lymphoma, chronic lymphocytic leukemia, metastatic gastric tumors), have a higher risk of having TB infection. TB infection (pulmonary and extra-pulmonary) occurs 2-9 times more than the general population in patients with hematological malignancies. In CML patients, treatment therapy with Imatinib posed a higher risk of development of TB due to defective cellular immunity. Co-administration of 1st line anti Tb medications mainly rifampicin with standard TKIs therapy Imatinib and Dasatinib has resulted in sub-therapeutic levels of these drugs due to induction of CYP4503A enzyme. Either by changing the TB treatment regimen to a non-rifampicin based therapy line with a combination of a fluoroquinolone, increasing the dose, or switching to a different TKI class may result in clinical improvement. To the best of our knowledge, there are no randomized control trials, or FDA approved guidelines to treat concomitant TB infection in CML patients. Therefore, a clear strategy to deal with such a clinical condition is lacking. The immediate treatment for the concomitant disease has been suggested based on clinical experience and clinical response of some patients published in few case reports, case series, and retrospective cohort studies. After careful literature review, we put forth our management proposals, However it need further research studies and clinical trials to bring recommendations and guidelines. Disclosures No relevant conflicts of interest to declare.

New techniques for quantification of color vision in disorders of cone function : Cambridge color test and photoreceptor-specific temporal contrast sensitivity in patients with heterozygous RP1L1 and RPGR mutations

HintergrundErbliche Netzhauterkrankungen mit Zapfendysfunktion können trotz relativ unauffälligem Fundusbefund ausgeprägte Visusminderung und deutliche Farbsinnstörungen aufweisen. Beispiele hierfür sind die autosomal-dominante okkulte Makuladystrophie (RP1L1-Gen) und die X‑chromosomale Retinitis pigmentosa (RPGR-Gen) – Letztere auch bei heterozygoten, weiblichen Merkmalsträgerinnen (Konduktorinnen). Neue Untersuchungsmethoden erlauben es, das Ausmaß der Farbsinnstörung zu quantifizieren.MethodenNach einer umfangreichen klinischen Untersuchung führten wir Messungen zur Quantifizierung der Farbdiskriminierung und der Zapfenfunktion durch. Beim Cambridge-Color-Test werden pseudoisochromatische Tafeln mit Landolt-C-Figuren computergesteuert generiert, um die Farbunterscheidungsschwelle entlang mehrerer Achsen im Farbraum zu bestimmen. Bei der Untersuchung der photorezeptorspezifischen zeitlichen Kontrastempfindlichkeit kann durch geschickte zyklische Veränderung der spektralen Zusammensetzung eines Lichtreizes die Kontrastwahrnehmungsschwelle isolierter Photorezeptortypen bestimmt werden. Die molekulargenetische Diagnostik erfolgte mithilfe von Next Generation Sequencing(NGS)-basierter gezielter Genpanelanalyse sowie Sanger-Sequenzierung.ErgebnisseBei 2 Patienten mit okkulter Makuladystrophie und 2 heterozygoten Trägerinnen von RPGR-Mutationen zeigten sich eine deutlich verminderte Fähigkeit zur Farbdiskriminierung und eine verminderte photorezeptorspezifische zeitliche Kontrastempfindlichkeit.DiskussionBei erblichen Netzhauterkrankungen sind neben den modernen bildgebenden Verfahren (okuläre Kohärenztomographie [OCT] und Fundusautofluoreszenz) auch die sinnesphysiologischen Untersuchungen diagnostisch wegweisend – der Nachweis von Farbsinnstörungen spielt hierbei eine wichtige Rolle. Neuere Methoden erlauben eine Quantifizierung der Farbsinnstörungen und könnten in klinischen Studien zu gen- und stammzellbasierter Therapie zur Messung des Therapieerfolges dienen.

What is color and how it is perceived?

The physical nature of color is well known and is based on its wavelength; however, the color perception in humans and animals is much less understood and is based mostly only on some assumptions and theories. We present the current knowledge on both of these topics, describe the anatomic basis for color vision, and discuss color vision deficiencies. Color vision disturbances can not only interfere with everyday activities but also impede performing specific professions. Commercial or military pilots, electricians, defense forces including paramilitary, food and art critics, and some physicians, scientists, and engineers may not be able to perform their professions to the full extent. Colors play an important role in the culture of various societies. The same color can have the opposite meaning in different cultures. Lack of knowledge of these meanings, when overcoming huge distances, is no longer a problem, but it can lead to unpleasant misunderstandings. Such cultural meanings of color are also discussed.

ASSESSMENT OF COLOR VISION FOR DIAGNOSIS AND DYNAMIC MONITORING OF MULTIPLE SCLEROSIS

Background: Multiple sclerosis is regarded as the most frequent cause of neurological disability. Visual disturbances are common and may be due to pathology of retina, optic nerve and cerebral conduction tracts (optic tract). Routine methods of assessment of visual function are insufficient in diagnosing some visual problems including color vision disturbances. Aim: To assess color vision in patients with multiple sclerosis. Materials and methods: We examined 110 patients (age > 18 years old) with previously diagnosed multiple sclerosis. Neurological status was assessed using functional scales; results of neuroimaging, medical records and history were taken into account. Color vision was examined using Farnsworth dichotomous test. Control group included 20 healthy volunteers (8 men, 12 women, mean age 29.1 ± 1.4 years old). Results: In patients with multiple sclerosis, color vision defects were significantly more prevalent compared to the control group (89.1% vs. 65%, p < 0.05). Deuteranopia was found in 18.6% of patients with multiple sclerosis, protanopia in 17.3%, tritanopia in 7.3% of patients. Significant color vision defects positively correlated with disability level of the Expanded Disability Status Scale (EDSS) and were independent of disease duration and history of retrobulbar neuritis. Conclusion: In patients with multiple sclerosis, color vision defects were associated with the activity of pathological process. Severity of neurological disability level estimated by EDSS positively correlated with visual disturbances. Thus, Farnsworth dichotomous test may be recommended for dynamic monitoring of multiple sclerosis.

Frequency and profile of Parkinson's disease prodromi in patients with malignant melanoma

ObjectiveThe results of register studies suggest an association between Parkinson's disease (PD) and melanoma. We studied the frequency and profile of early markers of PD in patients with malignant melanoma.Methods100...

Postoperative vision-related quality of life in macula-off rhegmatogenous retinal detachment patients and its relation to visual function.

ObjectiveTo determine the vision-related quality of life (VR-QOL) after surgery for macula-off rhegmatogenous retinal detachment (RRD) in relation to visual acuity, contrast acuity, and color vision.MethodsIn a prospective observational study, we included 55 patients with a macula-off RRD. Best corrected visual acuity (BCVA), color vision (saturated and desaturated color confusion indices (CCI)) and contrast acuity were measured at 12 months postoperatively in both the RRD eye and the fellow control eye, and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was filled out.ResultsOperated and fellow control eyes differed significantly in mean LogMAR BCVA (P<0.0001), median Log contrast acuity (P<0.0001), saturated CCI (P = 0.009), and desaturated CCI (P = 0.016). Significant correlations were observed between the NEI VFQ-25 overall composite score and postoperative LogMAR BCVA (R = −0.551, P<0.0001), contrast acuity (R = 0.472, P<0.0001), saturated CCI (R = −0.315, P = 0.023), and desaturated CCI (R = −0.283, P = 0.044).ConclusionsA lower VR-QOL was highly correlated to a worse postoperative BCVA and contrast acuity and to a lesser extent to color vision disturbances.

Color vision impairment in Parkinson's disease.

Acquired disturbances of color vision are a highly varied group of defects with frequent departures from established patterns. They can progress from normal trichromatism to anomalous trichromatism on to a dichromatic stage and to monochromatism where most color vision is lost, or they may be relatively stable [1]. A significant “modern effort” to present such conditions was published for first time in 1972 [2], attention was drawn in a significant account given 15 years later by Jaeger and Krastel emphasizing pharmaco-therapeutical effects [3]. Normally, dopaminergic neurons act in the outer and inner retina at multiple levels, producing alterations to the flow of visual information in a complex fashion. Dopamine is a chemical messenger for light adaptation, promoting the flow of information through cone circuits while diminishing that through rod circuits [4]. Color vision relies on the cone photoreceptor population and is therefore largely confined to the central retina. Because there is a segregation of color-specific information at the retinal into blue-yellow and red-green pathways, it is possible to use color discrimination tasks to assess cone and retinal ganglion cell subpopulations [4]. It has been reported that color vision is impaired in Parkinson’s disease (PD) [5] and some works have suggested that these disturbances to color vision affect predominantly the short-wave cone pathway [6]. Birch suggested that the acquired type three (tritan) defect at the retinal level as an early diagnostic sign of Parkinson’s ∗Correspondence to: Anna Piro, Neuroimaging Research Unit, IBFM-CNR, Germaneto, Catanzaro, Italy. Tel.: +393402529194; Fax: +39 0 9613695919; E-mail: anna.piro@cnr.it. disease [7]. We examined 49 PD Calabrian all male patients (age range, 50–85 years, mean age, 67 years) to avoid that genetic appearance of the “lionization” which can be present in the heterozygous females for color vision deficiency who mimic the vision of the normal females [8]. All patients underwent the L-DOPA doses subdivided into two different groups: 125–300 mg/day, low daily dose; 400–1000 mg/day, high daily dose. 25 age and sex matched controls showing a normal color vision, in comparison with the patients (chi square = 25.3, df = 1, p< 0.0005) were enrolled in comparison with 25/49 PD patients showing a defect of bleu/yellow axis. Controls did not show any PD signs, or other acquired ophthalmological disease. After informed consent, all patients, and controls had an examination by an ophthalmologist in order to rule a diabetic retinopathy, or a cataract, or an optic neuritis, or a senile maculopathy, or ocular fundus’ anomalies that could influence the color vision analysis. All PD patients who made more than 5 mistakes during their reading from the first 17 Ishihara plates were diagnosed as being color-blind, and this diagnosis was confirmed by their reading from the next four (numbers 18–21) Ishihara plates. The last four Ishihara plates (numbers 22–25) were utilized to define the type of color-blindness (the red or green colorbindness) and the grade of color-blindness: protanopy, the absence of red vision or protanomaly, the small deficiency of red color vision, and deuteranopy, the absence of green color vision or deuteranomaly, the small deficiency of green color vision [9]. PD colorblind patients were excluded from the analysis. So,

Acquired dyschromatopsia in acute myelocytic leukaemia

Patients with haematological malignancy are referred to the ophthalmologist either with visual symptoms or to exclude orbital or intraocular involvement after the diagnosis has been established. This report describes a patient with acute myelocytic leukaemia (AML) whose presenting symptom was dyschromatopsia. A 52-year-old female, previously in good health, presented with a disturbance of colour vision. On examination, there was bilateral reduction in visual acuity, impaired colour vision and severely constricted visual fields. Electrophysiological testing and colour contrast sensitivity (CCS) assessment were performed. CCS showed bilateral threshold elevation in the tritan axis of both eyes, right worse than left. Pattern ERG showed marked macular dysfunction in the right eye, but was normal in the left eye. Full-field ERGs fell within the normal range. Pattern VEPs were reduced in the right eye, without peak time shift; flash VEPs showed bilateral delay. Investigation showed severe anaemia, and a bone marrow biopsy confirmed a diagnosis of acute AML. There was symptomatic improvement in visual acuity and colour vision following blood transfusion and initiation of chemotherapy. This appears to be the first case report of dyschromatopsia in AML with symptomatic improvement following treatment. The case lends support to previously suggested hypotheses of chromatic visual disturbance in association with presumed hypoxia.

Treatment of Optic Neuritis

Optic neuritis (ON) is a self-limiting condition caused by inflammation-driven demyelination process affecting the optic nerve. Main clinical features are sudden, unilateral worsening of visual acuity, colour vision disturbance, visual field defects and motion-induced ocular pain. Spontaneous recovery appears usually within up to 8 weeks. It is a frequent initial manifestation of multiple sclerosis. Treatment of optic neuritis remains controversial, although many clinical trials have been conducted to establish firm therapeutic guidelines. The most relevant clinical trial is the Optic Neuritis Treatment Trial (ONTT), proving three days’ intravenous methylprednisolone therapy is not able to change the long-term prognosis, however improving visual recovery, what became a therapeutic option in monocular patients, patients with significant visual field loss, as well as those with professional requirements of fast visual recovery. The ONTT showed that 15-year risk of developing multiple sclerosis was 50 % regardless of the treatment regimen. Oral corticosteroids are recommended for treatment of acute optic neuritis.

Cone-rod dystrophy in Danon disease

In this issue, Thiadens and colleagues report ophthalmoscopic findings of macular disruption and physiologic findings of cone-rod dystrophy in two of four cousins from a family with Danon disease, a rare X-linked disorder characterized by muscle weakness, cardiomyopathy, and mental impairment, which has been mapped to mutations in the lysosomeassociated membrane protein gene, LAMP2 (OMIM #300257) [1]. Though descriptions of this disorder date from 1940 [2], there are only a handful of reports in the literature of ocular abnormalities [3–6]. The spectrum of the ocular findings remains unclear: the published reports are incomplete and the findings appear to differ markedly between families. For example, the report of LacosteCollin et al. [3] mentions “a diffuse chorio-capillary ocular atrophy,” but presents no details or fundus images. Prall et al. [5] report a “peripheral pigmentary retinopathy,” with “near-complete loss of pigment in the retinal pigment epithelium, ” and show images of peppered pigmentary mottling in affected females and an asymptomatic carrier, and complete loss of RPE pigmentation in an affected male, but provide no images of the posterior pole. They report prolongation of ERG latencies, but mention no reductions in amplitude. Schorderet et al. [6] show much milder pigmentary disturbance in two affected males, and asymmetric reduction in multifocal ERG amplitudes in one patient. In contrast, Thiadens et al. report predominantly central fundus abnormalities (a “bull’s-eye maculopathy”), severe color vision disturbances, and a cone-rod pattern of amplitude reduction in the full-field ERG. Their report is also of interest in expanding the spectrum of mutations linked to cone-rod dystrophies. OMIM lists at least 15 such disorders, of which three are X-linked. Of equal interest is the apparent variable expressivity in the present report, in which only two of four male cousins carrying the same LAMP2 mutation developed retinal symptoms. Much remains to be learned about both cone-rod dystrophies and about Danon disease and the pathogenetic implications of LAMP2 mutations.

An adaptive fuzzy-based system to simulate, quantify and compensate color blindness

About 8% of the male population of the world are affected by a determined type of color vision disturbance, which varies from the partial to complete reduction of the ability to distinguish certain colors. A considerable amount of color blind people are able to live all life long without knowing they have color vision disabilities and abnormalities. Nowadays the evolution of information technology and computer science, specifically image processing techniques and computer graphics, can be fundamental to aid at the development of adaptive color blindness correction tools. This paper presents a software tool based on Fuzzy Logic to evaluate the type and the degree of color blindness a person suffer from. In order to model several degrees of color blindness, herein this work we modified the classical linear transform-based simulation method by the use of fuzzy parameters. We also proposed four new methods to correct color blindness based on a fuzzy approach: Methods A and B, with and without histogram equalization. All the methods are based on combinations of linear transforms and histogram operations. In order to evaluate the results we implemented a web-based survey to get the best results according to optimize to distinguish different elements in an image. Results obtained from 40 volunteers proved that the Method B with histogram equalization got the best results for about 47% of volunteers.

Cone dystrophy with supernormal rod response – case report

Abstract Purpose Our purpose is to present a case demonstrating a novel, rare retinal disorder, called "cone dystrophy with supernormal rod response". Methods A 31‐year‐old female patient has been suffering from colour vision disturbances since her childhood. Her best corrected visual acuity is 0.2 in both eyes. Beyond routine ophthalmological methods we performed electrophysiological examinations, colour vision tests, dark adaptation, optical coherence tomography, fluorescein angiography and molecular genetic testing. Results Examinations revealed colour vision disturbances, OCT showed macular thinning, FLAG demonstrated enlarged foveal avascular zone. Electroretinography showed extinguished cone function, preserved rod response and supernormal maximal b‐wave. Genetic tests confirmed mutation of the KCNV2 gene. Conclusion "Cone dystrophy with supernormal rod response", known from recent literature, is a rare retinal disease, with the affection of the KCNV2 gene in the genetic background. Its stationery character is rare amongst cone dystrophies, congenital achromatopsia is the only one to have similar manifestation.

Perception Matches Selectivity in the Human Anterior Color Center

Human ventral cortex contains at least two visual areas selective for color [1]: a posterior center in the lingual gyrus labeled V4 [2-4], V8 [5], or VO-1 [6] and an anterior center in the medial fusiform that has been labeled V4alpha[3, 4]. We examined the properties of the anterior color center using electrical recording and electrical stimulation in a subject with an electrode implanted over the anterior color center, as determined with BOLD fMRI in the same subject. Presentation of visual stimuli evoked local field potentials from the electrode. Consistent with fMRI, the potentials were larger for chromatic than achromatic stimuli. The potentials differed depending on stimulus color, with blue-purple colors evoking the largest response. The spatial receptive field of the electrode was central/parafoveal with a contralateral bias. In the absence of a visual stimulus, electrical stimulation of the electrode produced an artificial visual percept of a blue-purple color near the center of gaze. These results provide direct evidence of a tight link between selectivity and perception in ventral temporal cortex. Electrical stimulation of the anterior color center is sufficient to produce the conscious percept of a color whose identity is determined by the selectivity of the stimulated neurons.

Post-marketing surveillance study of the efficacy and safety of vardenafil among patients with erectile dysfunction in primary care

To evaluate the safety and efficacy of vardenafil in primary care, we undertook a post-marketing surveillance study in 384 men with erectile dysfunction (ED), enrolled by 22 family physicians in Korea, from July 2004 to August 2005. Of the 384 patients enrolled, 343 (89.3%) returned for efficacy assessment and safety evaluation. Among the latter, 279 patients (81.3%) reported that their erectile function improved, 292 (92.1%) showed enhanced IIEF (International Index of Erectile Function)-5 scores and 265 (77.9%) responded that they were 'very satisfied' or 'satisfied' with vardenafil treatment. The most frequent reason for patient satisfaction with vardenafil was erectile potency (62.4%), followed by safety (42.4%), rapid onset (35.3%), adequate duration of efficacy (28.5%) and easy administration (25.9%). A total of 23 adverse events were observed in 18 patients, with the most frequent being hot flushes (3.2%), followed by headache (1.2%), nasal congestion (0.6%), color vision disturbance (0.3%), dizziness (0.3%), dry mouth (0.3%), dyspepsia (0.3%), nausea (0.3%) and diarrhea (0.3%). Only one patient discontinued vardenafil as a direct result of an adverse event. These results suggest that vardenafil prescribed by primary care physicians improved erectile function and was well tolerated by patients with ED.

Influence of learning effects on the results of the cap‐sorting test Roth 28‐hue (E) desaturated: Influence of learning effects on colour‐arrangement tests

AbstractThe results obtained in colour vision tests can be influenced by many factors. It is possible that a learning effect disguises the fact that an acquired colour vision disturbance has progressively either deteriorated or been successfully treated. Therefore, the primary object of this study was to examine whether a possible learning effect occurred if screening by the colour vision test Roth 28‐hue (E) desaturated was repeated several times, and if this learning effect was age dependent. Sixty‐five ocularly and generally healthy subjects participated in the study and were divided into two age groups: group A: 20–39 years, n = 35; group B: 40–59 years, n = 30. Besides their ophthalmological status (visual acuity, refraction, intraocular pressure, cup/disk ratio, central fundus), the cap‐sorting test Roth 28‐hue (E) desaturated was performed under standardized test conditions. The measurements were repeated after 5 ± 1.72 days (T1), 15 ± 3.53 days (T2), 32 ± 6.97 days (T3), and 189 ± 16.85 days (T4). The ophthalmological parameters of all subjects were inconspicuous. The individual evaluation of the error scores in the cap‐sorting test Roth 28‐hue (E) desaturated showed large‐scale variations. For both age groups there was no statistically significant difference between the right and left eye at any time. The mean values of the younger group remained relatively constant after the first measurement. This age group showed a quick, clearly visible learning effect that persisted over the whole test period. With regard to the older age group the average values deteriorated, remained solid for one month increasing again after 6 months. The results showed an age‐related learning effect. Therefore, it is important to repeat the colour vision test within 5 days for the age group 20–39 years. This second test result will then serve as a stable basis for further comparative examinations within a period of 6 months. The subjects of the age group 40–59 years ought to repeat a first colour vision test after 5 and again after 15 days. The result of the second repetition will then offer stable basic values for subsequent tests. © 2006 Wiley Periodicals, Inc. Col Res Appl, 32, 16–21, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.20282

A splice site mutation in the murine Opa1 gene features pathology of autosomal dominant optic atrophy

Autosomal dominant optic atrophy (adOA) is a juvenile onset, progressive ocular disorder characterized by bilateral loss of vision, central visual field defects, colour vision disturbances, and optic disc pallor. adOA is most frequently associated with mutations in OPA1 encoding a dynamin-related large GTPase that localizes to mitochondria. Histopathological studies in adOA patients have shown a degeneration of retinal ganglion cells (RGCs) and a loss of axons in the optic nerve. However little is known about the molecular mechanism and pathophysiology of adOA due to the lack of appropriate in vivo models. Here we report a first mouse model carrying a splice site mutation (c.1065 + 5G --> A) in the Opa1 gene. The mutation induces a skipping of exon 10 during transcript processing and leads to an in-frame deletion of 27 amino acid residues in the GTPase domain. Western blot analysis showed no evidence of a shortened mutant protein but a approximately 50% reduced OPA1 protein level supporting haploinsufficiency as a major disease mechanism in adOA. Homozygous mutant mice die in utero during embryogenesis with first notable developmental delay at E8.5 as detected by magnetic resonance imaging (MRI). Heterozygous mutants are viable and of normal habitus but exhibit an age-dependent loss of RGCs that eventually progresses to a severe degeneration of the ganglion cell and nerve fibre layer. In addition optic nerves of mutant mice showed a reduced number of axons, and a swelling and abnormal shape of the remaining axons. Mitochondria in these axons showed disorganized cristae structures. All these defects recapitulate crucial features of adOA in humans and therefore document the validity and importance of this model for future research.

Implanting a Clear Intraocular Lens in One Eye and a Yellow Lens in the Other Eye: A Case Series

To describe the color vision disturbance reported by patients in whom a clear intraocular lens (IOL) was implanted in one eye and a yellow-tinted (blue-light-absorbing) IOL in the other eye. Retrospective interventional case series. Data recorded included demographic information, dates of surgery, IOL model and power (manufacturer is the same for all lenses), best-corrected visual acuity, and subjective visual complaints. Four of five patients had no spontaneous color vision complaints. When these patients were informed of the unintended mismatch, all remarked that they could perceive a color vision difference, but that it was not bothersome. One of the five patients reported "beige" vision. None of the patients wanted an IOL exchange. Many patients can tolerate the color vision imbalance that results when a clear IOL is implanted in one eye and a yellow-tinted IOL is implanted in the other eye.

Novel Mutations in the OPA1 Gene and Associated Clinical Features in Japanese Patients with Optic Atrophy

Autosomal dominant optic atrophy (ADOA) is characterized by symmetrical bilateral optic atrophy associated with reduced corrected visual acuity (VA), central or centrocecal scotoma, and color vision disturbances. The disease is genetically heterogeneous, and the OPA1 gene has been identified as the only causative gene. The aims of this study were to identify and report mutations in the OPA1 gene in Japanese patients with ADOA and to describe the clinical features associated with the mutations. Molecular genetic study and observational case reports. Nine unrelated Japanese families with optic atrophy and 8 isolated cases of optic atrophy. Genomic DNA was extracted from peripheral leukocytes, and all exons containing the open reading frame of the OPA1 gene and the flanking intron splice sites were sequenced directly. Complete ophthalmologic examinations were performed. Direct sequencing of the OPA1 gene and clinical evaluations including VA, visual field, color vision, and disc appearance. Ten different heterozygous mutations, including 6 novel mutations, were detected in the OPA1 gene. The identified mutations included 5 deletions/insertions (c.2061delA, c.2098_2103delCTTAAA, c.2538insT, c.2591insC, and c.2708_2711delTTAG), 4 nonsense mutations (c.112C>T [p.R38X], c.181C>T [p.Q61X], c.946A>T [p.R316X], and c.2713C>T [p.R905X]), and 1 missense mutation (c.1635C>A [p.S545R]). The most common mutation in Caucasians (c.2708_2711delTTAG) was found in 3 unrelated families, suggesting that it is a mutational hot spot. We detected an OPA1 mutation in 8 of 9 familial cases of optic atrophy and in 4 of 8 cases that were initially considered to be sporadic from the patients' family histories. Examinations of family members of 2 sporadic probands revealed the existence of other family members with the OPA1 mutations whose phenotype was very mild or within normal limits. This indicates that patients with ADOA sometimes seem to be sporadic because of the extensive variation in the phenotype or, alternatively, a low penetrance of ADOA. OPA1 gene mutations are causative in most familial cases of ADOA in Japanese. Sporadic cases of optic atrophy frequently may be caused by OPA1 mutations in the Japanese population. Molecular genetic examinations are useful in determining the hereditary patterns in some cases of optic atrophy.