[Elderly people with visual impairment in The Netherlands]. / Visuele beperkingen bij ouderen in Nederland--risicogroepen en mogelijkheden tot interventie.

AIM: To estimate the number of elderly people with visual impairment in The Netherlands, now and in the future. Possibilities for intervention are discussed. METHODS AND MATERIALS: Estimates are based on a recent report on behalf of Foundation InZicht, ZonMw, in which prevalence data from population-based studies on blindness and low vision and its causes in The Netherlands, western Europe, The United States and Australia are related to the latest demographic data for The Netherlands. RESULTS: Of the 16.4 million Dutch in 2008 2.4 million (14.7%) are 65 years of age and older. Of this last group 155,000 persons are living in nursing homes or residential homes, the others are living in their own homes. In 2008 an estimated 77,000 persons are blind and 234,000 have low vision. Of them 79% is 65 years of age or older. Of the older people in care institutions 20% is blind (32,000) and 22% has low vision (34,000). In 62% of them the visual impairment is treatable or could have been prevented ('avoidable'). Of the older people living independently 1.2% is blind (27,000) and 6.8% has low vision (154,000). In 57% of them the affliction is avoidable. CONCLUSION: In 2008 247,000 elderly suffer from a visual impairment that could have been treated or prevented in 143,000 (58%) of them. Screening and treatment of elderly in care institutions seems indicated, as is health education to and goal-oriented screening of elderly who live independently.

[Learning to see things from a different perspective: interns and residents collaborate with artists to become better doctors]. / Anders leren kijken en de ander leren zien.

In 2016 and 2017, we started an innovative learning track in the Radboudumc that combines arts and medical education, and appraised the learning processes involved. The voluntary track was followed by 32 and 30 participants respectively, mostly interns and a few residents. The initiative built upon the ideas of several American educational developments which incorporated museum visits. We extended the format by having participants join artists in their studios, to allow students to have an immersive experience of a different discipline, rather than only observing its end products. The track did not have specific learning objectives. However, participants were encouraged to set personal goals and to reflect on what they learned in terms of observation skills, creative thinking, personalized health care, and frame reflection. Here we report the rationale of the track, and illustrate preliminary conclusions with participants' quotes.

Normal HLA class I, II, and MICA gene distribution in uveal melanoma.

PURPOSE: The molecules of the HLA class I and II molecules as well as the MHC class I chain-related gene A (MICA), a polymorphic and stress-induced cell surface molecule, are involved in T-cell and natural killer-cell (NK-cell) mediated immune responses. In this study we looked for any genetic susceptibility contributed by HLA class I, class II, or MICA genes with regard to the development of uveal melanoma. METHODS: Between 1998 and 2001, 159 uveal melanoma patients were typed for HLA class I and II, and 168 uveal melanoma patients were evaluated for MICA by microsatellite typing. The HLA antigen and MICA allele frequencies were compared with control groups of, respectively, 2,440 and 247 healthy Dutch individuals. RESULTS: HLA class I, HLA class II, and MICA gene frequencies in uveal melanoma patients and healthy Dutch controls showed no significant deviations after correction for the number of comparisons. CONCLUSIONS: We conclude that there is no genetic susceptibility or increased risk attributed to any HLA class I, class II, and MICA polymorphism with regard to the development of uveal melanoma.

Thermotherapy in the management of choroidal melanoma.

During the past 20 years of enucleation, which was the standard treatment for choroidal melanoma over more than a century, has largely been replaced by eye salvaging therapies such as radiotherapy or local resection. In 1995 transpupillary thermotherapy (TTT) using an infrared diode laser was introduced as a new conservative therapy for patients with choroidal melanoma. TTT can be defined as a heat treatment modality, which is delivered through a dilated pupil to the tumour surface. The technique uses a wide diode laser beam diameter with a low irradiance and a long exposure time. TTT induces tumour necrosis at sub-photocoagulation levels by a direct cell destructive effect with only a few ocular complications. TTT can be performed as sole therapy or combined with plaque radiotherapy, thus permitting a lower radiation dose. For amelanotic tumours dye-enhanced TTT with indocyanine green can be used. In this paper we review the role of sole or combined TTT, related to the current other treatment modalities for choroidal melanoma.

[Avoidable visual impairment in The Netherlands: the project "Vision 2020 Netherlands" of the World Health Organization]. / Vermijdbare slechtziendheid in Nederland: het project 'Vision 2020 Netherlands' van de Wereldgezondheidsorganisatie.

In the year 2004 there were an estimated 220,000-320,000 people in The Netherlands with visual impairment. In 150,000-220,000 (70%) of them the visual impairment is either curable or could have been prevented. Those most at risk are people with intellectual disabilities, elderly people in care institutions, elderly people in general and diabetics. 'Vision 2020 Netherlands', an initiative of the World Health Organization, was launched to eliminate avoidable visual impairment in the Netherlands by the year 2020 by means of awareness campaigns, implementation of screening programmes and by expanding eye care capacity through efficient cooperation between the professional groups involved in eye care.

Density of foveal cone pigments at older age.

We investigated foveal cone photopigment kinetics by retinal densitometry in 34 eyes of 29 healthy subjects with clear optical media and good visual acuity, ranging in age from 39 to 79 years. Our aim was to assess possible senile disturbances of foveal cones. To assess the effects of ocular straylight, we measured not only in subjects with a clear crystalline lens, but also in pseudophakia and aphakia. In a limited number of subjects color vision was assessed with a Nagel anomaloscope; no systematic changes with age were found. A significant decrease in two-way density and in time constant of regeneration was found to occur only after age 60, with large individual variations. There was no indication that results for subjects with their natural crystalline lens, in aphakia, or in pseudophakia were different. We argue that a reduction in the number of cones with age, rather than an increase in ocular stray light is the most likely explanation of our findings.

Retinal densitometry in acute posterior multifocal placoid pigment epitheliopathy.

Cone photopigment kinetics were investigated by retinal densitometry in six patients with acute posterior multifocal placoid pigment epitheliopathy (APMPPE). Our goal was to document the course of cone impairment during a period of at least 12 months following the onset of the disease process. During the active stage, we found that the amount of pigment measurable by densitometry (the density difference) was reduced and that the time constant of pigment regeneration was unmeasurable. Following resolution of the fundus lesions, the densitometric parameters gradually improved in eight of ten eyes. In patients who maintained foveal fixation (five eyes), the density difference and the time constant of pigment regeneration improved simultaneously, though with individual differences in time course. Photopigment kinetics returned to normal in all these patients but the density difference remained lower than normal in four of the five eyes. In patients with parafoveal fixation (five eyes), photopigment kinetics were slow, possibly reflecting mixed cone and rod contributions. With time, the density difference improved to a level comparable to that measured in normal observers at a similar retinal location, but the photopigment regeneration time constant remained abnormal or unmeasurable. Recovery was variable, with one eye changing from parafoveal to foveal fixation, and no improvement noted in two eyes with extreme parafoveal fixation. Our findings demonstrate a large interpatient variation associated with APMPPE.

Rod densitometry in the aging human eye.

Retinal densitometry is a noninvasive physiologic technique used to examine the visual pigments in living human eyes. To assess possible age-related disturbances of rod photopigment kinetics, retinal densitometry was done in 44 eyes of 44 healthy subjects (age range, 12-78 yr). With progressing age, a significant but small increase in photopigment density difference (bleached versus dark adapted eye) and an increase in the time constant of rhodopsin regeneration was found. The increased density difference in rods was consistent with morphologic findings of increased rod outer segment diameter and disc content in older subjects. To explain this change in terms of the decreased specular reflections at the level of the inner limiting membrane was inadequate because age effects were independent of wavelength in the region of 450-550 nm. To control for the effects of ocular stray light from the lens, subjects older than 40 yr with a clear crystalline lens were measured and compared with those with pseudophakia. No statistically significant difference was found between the two groups. Increased rod density difference contrasts sharply with an earlier reported decrease in this parameter for foveal cones. The slowing of the regeneration rate is a phenomenon common to rods and cones. It may be a result of a gradual metabolic dysfunction of the retinal pigment epithelium in older subjects.

Expression of epidermal growth factor receptor: risk factor in uveal melanoma.

PURPOSE: To investigate the prognostic significance of the expression of epidermal growth factor receptor (EGFR) in uveal melanoma. EGFR is a transmembrane glycoprotein, and its expression has been correlated with the development of metastases in various malignancies. METHODS: Frozen sections from 22 primary uveal melanomas were examined for EGFR expression by a three-step immunoperoxidase staining, using a mouse anti-human EGFR IgG2b monoclonal antibody. The results were compared with patient survival and clinical and histopathologic parameters. RESULTS: EGFR expression could not be determined on one tumor due to excessive pigmentation. Two patients died of causes unrelated to melanoma, and two patients were lost to follow-up. Out of 21 tumors, six tumors showed immunoreactivity for EGFR. Five of these six patients (83%) died due to metastases, compared with 2 (17%) of 12 patients with no EGFR expression (Kaplan-Meier analysis P = 0.0004). EGFR-positive tumors tended to have a greater tumor prominence and a higher mitotic rate. CONCLUSIONS: The expression of EGFR was significantly correlated with death due to metastatic disease and therefore can be regarded as an important prognostic factor in human uveal melanoma.

Characterization of melanocortin-1 receptor gene variants in uveal melanoma patients.

PURPOSE: Allelic variations of the melanocortin-1 receptor (MC1R) gene have been linked to red hair and sun-sensitive skin types and may play a role in the susceptibility to develop cutaneous malignant melanoma (CMM). To define the role of MC1R gene in uveal melanoma, a case control study was performed, in which the presence of MC1R gene variations in uveal melanoma patients was compared with that of healthy controls. METHODS: MC1R gene variants were analyzed in 162 uveal melanoma patients and 255 healthy controls. After genomic DNA was isolated from venous blood, the MC1R gene was amplified by polymerase chain reaction (PCR) and examined for the presence of variants by single-strand conformation polymorphism (SSCP) analysis. Participants were asked to complete a questionnaire regarding skin type, eye color, and hair color. RESULTS: No disparity was found between the distribution of the MC1R gene variants in both groups. Furthermore, no associations between MC1R genotype and pigment phenotype were found. In contrast to CMM, uveal melanoma patients did not show specific MC1R gene variants. Compared with controls, most uveal melanoma patients had blue eyes (65%, P = 0.060) and skin type III (56%); however, in the uveal melanoma group the presence of dark blond hair was significantly elevated (46%, P = 0.030). These findings are in contrast with studies on CMM, where most patients have skin type II and red/fair hair. CONCLUSIONS: These data suggest that MC1R variants do not play a role in the susceptibility to develop uveal melanoma. Furthermore, most uveal melanoma patients share phenotypic characteristics that differ from findings in CMM patients.

Transpupillary thermotherapy: results in 50 patients with choroidal melanoma.

OBJECTIVE: To evaluate the efficacy and safety of transpupillary thermotherapy in treating choroidal melanoma. METHODS AND PATIENTS: To perform transpupillary thermotherapy, infrared diode laser energy at 810 nm was used with a beam diameter of about 3 mm and 1-minute exposure time. All 50 patients had choroidal melanoma. We performed transpupillary thermotherapy in 21 tumors that had responded insufficiently to 800 Gy ruthenium 106 brachytherapy; it was combined with 800 Gy106Ru brachytherapy for 10 tumors greater than 5 mm in height and with 600 Gy for 19 tumors 5 mm or less in height. RESULTS: All but 1 tumor exhibited reduction in tumor height within a mean follow-up of 20.5 months (range, 6-49 months). In 41 eyes (82%), the tumor flattened completely. Visual acuity was 20/60 or better in 43 eyes (86%) before treatment and in 14 eyes (28%) at the last examination because of radiation vasculopathy. Neovascular glaucoma developed in 1 eye, and total retinal detachment developed in 2 eyes. Tumor recurrence was observed in 1 patient. CONCLUSIONS: Although long-term results are necessary to properly appraise this new therapy, transpupillary thermotherapy may be useful as a complementary modality to brachytherapy.

Mizuo phenomenon in X-linked retinoschisis. Pathogenesis of the Mizuo phenomenon.

Four unrelated males with X-linked retinoschisis and a golden fundus reflex had Mizuo-Nakamura phenomenon, which, to our knowledge, has been described only in Oguchi's disease and X-linked cone dystrophy. These findings, together with experimental observations and data from the literature, led us to hypothesize that the Mizuo-Nakamura phenomenon is caused by an excess of extracellular potassium in the retina as a result of a decreased potassium scavenging capacity of retinal Müller cells.

Color matching and foveal densitometry in patients and carriers of an X-linked progressive cone dystrophy.

We describe a family with an as yet undescribed form of X-linked progressive cone dystrophy in a five-generation pedigree, from which we report here the results of 17 male patients and 31 obligate and 13 possible female carriers. The affected males showed the characteristic picture of cone dystrophy. Foveal cone photopigment density was impaired (judged from anomaloscope settings and foveal densitometry), even at an early stage of the disease. The carriers showed no fundus abnormalities, except occasional changes due to myopia. The anomaloscope demonstrated mild pseudoprotanomaly in 27 of 31 obligate carriers and in six of 13 possible carriers. Foveal densitometry findings performed in 11 carriers always agreed with the anomaloscope findings. We conclude that the findings of pseudoprotanomaly and abnormal density differences in females of this family were the only ocular abnormalities and thus are indicative of the carrier state.

Clinical applications of fundus reflection densitometry.

Fundus reflection densitometry or retinal densitometry is a non-invasive technique to examine the visual photopigment kinetics in living eyes. The technique is based on the comparison of the reflected light from the fundus in a fully light adapted eye (when all visual photopigment has been bleached) with the reflected light following complete dark adaptation (when the retina contains its maximum amount of visual photopigment). The technique provides a measure of the density of visual photopigment, its time constant of regeneration, its distribution and spectral characteristics if measured at a series of wavelengths. Fundus reflection densitometry in the human eye was introduced 40 years ago. Presently, it is the only available technique from which direct and objective insight can be obtained into visual photopigment. This knowledge is particularly relevant in eyes where abnormalities of photoreceptor function are suspected. This paper summarizes the current knowledge of fundus reflection densitometry in the diseased and in the aging human retina, gathered over the last 30 years. Considerable improvements of the instrument for clinical purposes have been obtained, and are also discussed.

Phase I study using desferrioxamine and iron sorbitol citrate in an attempt to modulate the iron status of tumor cells to enhance doxorubicin activity.

A novel approach to enhance the activity of doxorubicin is to increase the availability of cellular "chelatable" iron to participate in doxorubicin-mediated free-radical generation. To achieve this, we designed a regimen consisting of desferrioxamine (DFO, 50 mg/kg daily given as an i.v. infusion over 72 h) to increase cellular iron uptake. Thereafter, the combination of iron sorbitol citrate (ISC) and doxorubicin (as a single agent or as part of the CHOP regimen) was given. In a phase I study we investigated the toxicity of this regimen in nine patients with refractory malignant disease. Severe but reversible ocular toxicity (i.e., acute maculopathy) was observed in two patients. As these patients were the only ones who were pretreated with cisplatin, we caution against the use of DFO in cisplatin-pretreated patients. Severe phlebitis was encountered in five of nine patients. A partial remission was observed in two of four patients with refractory Non-Hodgkin's lymphoma who were treated with DFO, ISC, and doxorubicin as part of the CHOP regimen. We conclude that pretreatment with DFO and iron sorbitol citrate may be of benefit in the treatment of malignancies with doxorubicin-containing regimens, but ocular toxicity and severe phlebitis limits the use of DFO in this approach. The attachment of DFO to biocompatible polymers may be a method of overcoming the observed toxicity and warrants further study.

Foveal densitometry in adult-onset diffuse drusen.

We compared the results of foveal densitometry with results of other retinal function tests in five asymptomatic subjects with adult-onset diffuse drusen. All results of routine retinal function tests, including visual acuity, Rayleigh equation color matches, multiple static perimetry, electroretinography, and electro-oculography, were normal. All five subjects had decreased foveal cone photopigment density with densitometry, indicating an early dysfunction at the level of the foveal cone photoreceptors. Several functional defects may be responsible for the densitometric results in adult-onset diffuse drusen, including retinal pigment epithelium dysfunction, foveal cone photoreceptor misalignment, and a reduction of the in situ foveal cone photopigment.

Scanning laser densitometry in visual acuity loss of unknown origin.

AIM: To assess foveal cone photoreceptor function in patients with unexplained loss of central visual acuity. METHODS: Testing of foveal cone photoreceptor function was performed using scanning laser densitometry, colour matching (Rayleigh equation), and pattern electroretinography (ERG). Standard tests included full field ERG, electrooculography, visual evoked potentials, static perimetry, and fluorescein angiography. RESULTS: Decreased foveal cone photopigment density and abnormal pattern ERG were found in three patients. Results of colour matching were not unequivocal. CONCLUSION: Testing of foveal cone photoreceptor function using scanning laser densitometry may determine the location of pathological changes in certain patients with unexplained visual loss.

Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes.

BACKGROUND: It has been suggested that eating green leafy vegetables, which are rich in lutein and zeaxanthin, may decrease the risk for age related macular degeneration. The goal of this study was to analyse various fruits and vegetables to establish which ones contain lutein and/or zeaxanthin and can serve as possible dietary supplements for these carotenoids. METHODS: Homogenates of 33 fruits and vegetables, two fruit juices, and egg yolk were used for extraction of the carotenoids with hexane. Measurement of the different carotenoids and their isomers was carried out by high performance liquid chromatography using a single column with an isocratic run, and a diode array detector. RESULTS: Egg yolk and maize (corn) contained the highest mole percentage (% of total) of lutein and zeaxanthin (more than 85% of the total carotenoids). Maize was the vegetable with the highest quantity of lutein (60% of total) and orange pepper was the vegetable with the highest amount of zeaxanthin (37% of total). Substantial amounts of lutein and zeaxanthin (30-50%) were also present in kiwi fruit, grapes, spinach, orange juice, zucchini (or vegetable marrow), and different kinds of squash. The results show that there are fruits and vegetables of various colours with a relatively high content of lutein and zeaxanthin. CONCLUSIONS: Most of the dark green leafy vegetables, previously recommended for a higher intake of lutein and zeaxanthin, have 15-47% of lutein, but a very low content (0-3%) of zeaxanthin. Our study shows that fruits and vegetables of various colours can be consumed to increase dietary intake of lutein and zeaxanthin.

Corneal autofluorescence in choroidal melanoma or in choroidal naevus.

AIMS: To investigate whether corneal autofluorescence is different in patients with choroidal melanoma or choroidal naevus. METHODS: Corneal autofluorescence was determined by fluorophotometry in both eyes of 32 patients with a unilateral choroidal melanoma, 32 patients with a unilateral choroidal naevus, and 32 age matched healthy controls. The corneal autofluorescence ratio between affected and contralateral eyes of patients or between randomly selected eyes of healthy controls was calculated. RESULTS: Mean corneal autofluorescence ratio of patients with a choroidal melanoma was significantly higher than that of healthy controls (mean ratio: 1.09 (SD 0.15) and 1.00 (0.09), respectively, ANOVA p=0.014), and than that of patients with choroidal naevus (mean ratio 0.96 (0.09), p<0.001). Mean ratios of patients with choroidal naevus and healthy controls were not significantly different (p=0.27). CONCLUSIONS: Corneal autofluorescence ratio of patients with a unilateral choroidal melanoma is increased. This is probably due to an increased flow of glucose through the impaired blood-aqueous barrier in the affected eye, resulting in additional glycation of corneal proteins and hence in increased autofluorescence. The corneal autofluorescence is not increased in patients with a choroidal naevus, because the blood-aqueous barrier is not impaired in the affected eye in these patients. Measurement of corneal autofluorescence is simple, fast, and non-invasive, and might be helpful to distinguish between patients with choroidal melanoma and those with choroidal naevus.

HLA expression in a primary uveal melanoma, its cell line, and four of its metastases.

BACKGROUND: The level of HLA expression on a tumour may influence the immunological response against this tumour, and vice versa. HLA expression was determined in a primary uveal melanoma, its metastases, and on a cell line derived from this melanoma, and the presence and type of infiltrate in tissue sections were also studied. METHODS: Immunohistochemistry with monoclonal antibodies (MAbs) against HLA class I and II, T cells, NK cells, and macrophages. RESULTS: Primary and metastatic lesions, as well as the cell line showed high levels of expression of the monomorphic determinants of HLA class I. Expression of the polymorphic HLA-A2 and HLA-A3 antigens was decreased on metastases to the skin and liver. HLA-Bw4 expression was low on all lesions, as well as expression of HLA class II. Tumour infiltrating cells consisted mainly of CD3, CD4, and CD8 positive cells. Expression on the cell line corresponded to expression on the primary tumour. CONCLUSION: The primary uveal melanoma as well as the cell line showed a high expression of monomorphic and polymorphic HLA-A antigens, while metastases showed a high expression of monomorphic and a lower expression of polymorphic antigens. This variation in expression may support tumour cell escape from NK cells as well as CTL mediated lysis.