[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.

[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.

S-100B protein and melanoma inhibitory activity protein in uveal melanoma screening. A comparison with liver function tests.

AIM: Our purpose was to determine whether S-100B or melanoma inhibitory activity (MIA) concentrations in the serum of patients with large uveal melanomas were better markers for the presentation of metastases than liver function tests. We also investigated whether increased marker levels were related to known clinical and histopathological prognostic parameters. METHODS: Total S-100B (A1B + BB) and MIA concentrations were measured in the sera from 104 patients with uveal melanoma prior to enucleation and in the sera from 50 healthy controls. Concentrations were also determined in the sera from 30 patients with known uveal melanoma metastases. Liaison Sangtec 100, an automated immunoluminometric assay measuring the total S-100B, and Roche MIA ELISA were used to quantify these proteins in serum. Results were compared with liver function tests [alkaline phosphatase, lactate dehydrogenase (LD), aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase]. RESULTS: The mean S-100B and MIA concentrations were significantly higher in patients with metastases compared to melanoma patients without metastases. At the time of enucleation, S-100B and MIA were not prognostic for metastases in uveal melanoma, but S-100B and LD were the best tests to predict the occurrence of metastatic disease during the follow-up period. CONCLUSIONS: In our study, the S-100B and MIA serum concentrations were not correlated with any tested established prognostic parameter. S-100B and LD showed better performance in identifying melanoma metastases than gamma-glutamyl transpeptidase and MIA. A prospective follow-up study is needed to evaluate S-100B and MIA in identifying early micrometastasis in uveal melanoma.

Single spot PDT in patients with circumscribed choroidal haemangioma and near normal visual acuity.

BACKGROUND: In circumscribed choroidal hemangiomas (CCH) a long observation period and decreased visual acuity before treatment are risk factors for poor visual outcome. Therefore, we studied the use of limited, single spot photodynamic therapy (PDT) with Visudyne for the timely treatment of CCH. METHODS: Six consecutive patients with CCH, and metamorphopsia but (near) normal visual acuity were treated with PDT, using a single spot covering only the most prominent part of the tumour, and a radiance exposure of 50 J/cm(2). Start of treatment was 6 min following a 1-min infusion with Visudyne (6 mg/m(2) BSA), using a diode laser (692 nm). RESULTS: In all patients, the metamorphopsia disappeared, the OCT images returned to a normal foveal contour, and visual acuity remained 20/20 or improved to 20/20. In five patients, the tumour became ultrasonographically undetectable; in three after one PDT session, in one patient after two and in another patient after three PDT sessions. The last patient had a residual tumour height of 1.2 mm, but no metamorphopsia, a normal foveal contour on OCT, and fluorescein angiography showed no residual leakage. CONCLUSION: The present series demonstrates that single spot PDT might be an effective treatment for CCH with a visual acuity > or =20/30, without serious side-effects during a follow-up of at least 18 months.

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.

Prevention of blindness in leprosy and the role of the Vision 2020 Programme.

Leprosy control programmes are highly successful. As a result, leprosy control will be more and more integrated into the general health services. The existing vertical, specialized control programmes will be dismantled. Eye complications in leprosy have decreased. This is a result of earlier diagnosis and highly effective multidrug treatment (MDT) of leprosy, combined with timely treatment of secondary nerve damage by steroids. Most ocular morbidity is now found among elderly and disabled leprosy patients who were diagnosed before effective MDT treatment became available. Many of these patients live in leprosy settlements. Age-related cataract has become the leading cause of blindness in leprosy. The second cause of blindness is corneal opacification, mainly as a result of neglected exposure keratitis and corneal anaesthesia. The miotic pupils in late multibacillary leprosy, in combination with small central lens opacities, may also lead to blindness. The Vision 2020 Initiative prioritises cataract surgery. Leprosy patients should be actively included. Disabled leprosy patients can also benefit from screening programmes for refractive errors and the provision of spectacles and low vision aids. Determining the most feasible surgical methods for lagophthalmos surgery remains a challenge. For all health and eye care staff, training in leprosy and its eye complications is needed, as well as a change in attitude towards leprosy patients. Staff must be prepared to welcome them in the general health services.

[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.

Screening for uveal melanoma metastasis. Literature review.

Local tumour control in uveal melanoma has improved in the last decades. However, 5-year mortality due to metastases from large uveal melanomas remains high. Recently both isolated liver perfusion therapy and chemotherapy have reached encouraging results in improving metastasis survival. As such screening at an early stage, especially for liver metastases, becomes imperative.

Combined plaque radiotherapy and transpupillary thermotherapy in choroidal melanoma: 5 years' experience.

AIM: To evaluate the results of combined plaque radiotherapy and transpupillary thermotherapy (TTT) in 50 consecutive patients 5 years after treatment. METHODS: 50 adult patients with choroidal melanoma were treated with ruthenium-106 ((106)Ru) plaque radiotherapy combined with TTT. A flat scar was the preferred end point of treatment. The mean tumour thickness was 3.9 mm (range 1.5-8.0 mm), the mean tumour diameter was 11.3 mm (range 5.8-15.0 mm). TTT was performed with an infrared diode laser at 810 nm, a beam diameter of 2-3 mm, and 1 minute exposures. Tumours >5 mm thick received an episcleral contact dose of 800 Gy (106)Ru; tumours 3 mm thick (log rank test p = 0.01). Eight melanomas were amelanotic, seven of which required multiple TTT sessions. In one patient the tumour recurred at the central margin of the treated area; this eye was enucleated. In one patient the tumour failed to regress 6 months after treatment and enucleation was performed at the patient's request. Three eyes developed severe proliferative retinopathy. Radiation maculopathy caused a loss of the best corrected visual acuity: before treatment 31 patients had a best corrected visual acuity of 20/60 or better but in only 12 patients did it remain in this range 5 years after treatment. Three patients developed distant metastasis to the liver. CONCLUSION: The 5 year results for combined plaque radiotherapy and TTT as treatment for choroidal melanoma are favourable in terms of complete tumour regression and low rate of recurrences; however, there was considerable loss of visual acuity as a result of radiation maculopathy.

Longstanding symptomatic choroidal hemangioma managed with limited PDT as initial or salvage therapy.

PURPOSE: To describe the use of limited, low-irradiance, single-spot photodynamic therapy (PDT) with verteporfin for the treatment of symptomatic choroidal hemangiomas. METHODS: Thirteen consecutive patients with a circumscribed choroidal hemangioma were treated with limited PDT 6 min following a 1-min infusion with verteporfin (6 mg/m(2) body surface area), using a diode laser (692 nm) and a single spot large enough to cover only the most prominent part of the tumor. Exposure time was 166 s in the first three patients and 83 s in the last ten patients, resulting in a radiance exposure of respectively 100 and 50 J/cm(2). RESULTS: In all 11 not previously conventionally treated patients, visual acuity improved following PDT treatment. The two remaining patients with prior radiation treatment both reported widening of the visual field and sharper vision, but did not show an increase in ETDRS vision. In all but four patients the tumor became ultrasonographically undetectable by the first follow-up visit at 6 weeks, with only a slight irregularity at the level of the previous tumor remaining. In four patients the residual tumor was still detectable, and they received a second treatment, following which the tumor flattened completely. In all patients the retinal detachment disappeared. CONCLUSION: The present series demonstrates that even limited, low-irradiance, single-spot photodynamic therapy with verteporfin is an effective first-line treatment for choroidal hemangiomas.

Short communication: Effects of subacute ruminal acidosis on free-choice intake of sodium bicarbonate in lactating dairy cows.

The effect of inducing subacute ruminal acidosis (SARA) on the free-choice intake of sodium bicarbonate (SB) was investigated in four midlactation Holstein cows in a switchover experiment with four 1-wk periods. The SARA was induced by replacing 25% of the ad libitum intake of total mixed ration (TMR) with pellets containing 50% ground wheat and 50% ground barley and restricting access to TMR from 0700 to 1700 h. Control consisted of feeding TMR ad libitum. Powdered SB was provided for ad libitum consumption. Rumen pH was measured continuously using indwelling pH probes. Induction of SARA reduced (P < 0.05) the average daily rumen pH from 6.08 to 5.87, increased (P < 0.05) the average duration of rumen pH below 6 from 547 min x d(-1) to 916 min x d(-1), and increased (P < 0.05) the average duration of rumen pH below 5.6 from 132 min x d(-1) to 397 min x d(-1) (P < 0.05) but did not significantly affect SB intake. Average intake of SB was 26.8 g x d(-1) during SARA and 34.5 g x d(-1) during control. These low SB intakes must not have substantially affected rumen pH. Sodium bicarbonate intake differed significantly (P < 0.05) between cows. These data indicate that cows did not select SB in order to attenuate SARA.

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.

Effects of a subacute ruminal acidosis model on the diet selection of dairy cows.

Two experiments were conducted to study the effects of a subacute ruminal acidosis (SARA) model on diet choice in dairy cows. In the first experiment, 25% of the ad libitum dry matter intake (DMI) of the total mixed ration (TMR) was replaced with wheat-barley pellets (WBP, 50% ground wheat, 50% ground barley). Rumen pH was measured continuously via in-dwelling probes in 4 mid to late lactation cows. This diet change reduced rumen pH by 0.14 +/- 0.02 pH units (mean +/- SE) and increased time below pH 6.0, from 319 +/- 36 min(-1) to 641 +/- 36 min(-1). Hence, the nutritional model successfully induced SARA. The second experiment determined if inducing SARA increases the feed preference for long alfalfa hay compared with alfalfa pellets. The 2 wk of inducing SARA were separated by 1 control wk. Four cows on either SARA and control diets were given a choice of 2 feeds, 2 times per d, for 30 min. The preference ratios (PR = Amount of Hay consumed/Amount of Hay + Pellets consumed) for alfalfa hay during two SARA weeks was greater (0.85 +/- 0.03) compared with the control week (0.60 +/- 0.03). In SARA weeks, average rumen pH was 0.23 +/- 0.03 units lower, and time below pH 6.0 and 5.6 was higher compared to control. These results suggest that when given a choice of feeds, dairy cows alter their diet selection to attempt to attenuate SARA.

Additional cell damage after transpupillary thermotherapy in choroidal malignant melanoma.

The aim of this study was to evaluate the effectiveness of transpupillary thermotherapy (TTT) in generating tumour necrosis by light and electron microscopy, as well as to evaluate additional cell damage in the area directly adherent to the necrotic zone. Four eyes of four patients diagnosed with intraocular malignant melanoma of the uvea were treated experimentally with diode laser TTT. In all cases a standard technique was used. All eyes were enucleated: one eye the day after TTT, two eyes 2 days after TTT, and one eye 6 weeks after TTT. Immediately after enucleation the eyes were immersed in standard Karnovsky's fixative with cocodylate buffer and prepared for light and electron microscopy. In the treated area of all four melanomas we found a dense band of necrotic tissue (zone A) consisting of an amorphous mass of dead cells sharply demarcated from the rest of the neoplastic tissue. Next to this zone was a more eosinophilic and also sharply demarcated band (zone B) that consisted of similar but less intensive changes. In the next band (zone C), marked injury to the cellular membrane and subcellular structures were seen on electron microscopy. The next band (zone D) consisted of changes mainly observed only within the cytoplasm of neoplastic cells and significantly less intensive than those in zone C. Outside zone D tumour cells that were normal in appearance were seen. No scleral alterations induced by heat were found. We concluded that after TTT the cytotoxic effect gradually decreases in proportion to the distance from the central point of the diode laser spot, with additional cell damage in the area adjacent to the necrotic zone. The interval between TTT and enucleation had no influence on the histological results.

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.

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.

Temperature dependence of thermal damage to the sclera: exploring the heat tolerance of the sclera for transscleral thermotherapy.

Thermal damage to the human sclera in relation to temperature and duration of exposure was studied in order to determine the heat tolerance of the sclera with respect to transscleral thermotherapy of choroidal melanoma. Samples of human sclera were submerged in saline for 10 sec to 10 min at temperatures of 37-100 degrees C. The effects of heat on the shape, weight and size of the samples were studied. Thermal damage of scleral collagen was examined by polarized light microscopy (LM) and electron microscopy (EM). The sclera was embedded in epoxy resin and stained with toluidine blue for LM and with uranyl acetate and lead citrate for EM. Thermal damage of scleral collagen on polarized LM was graded on a five point scale. Scleral damage was visible on macroscopic examination and on LM and EM in sclera heated at 65 degrees C for 20 sec or longer, at 70 degrees C for 10 sec or longer, and at higher temperatures. A sigmoidal function was used to define the relation between temperature and changes in diameter, thickness, and weight of scleral samples. Using fitted functions, the threshold temperature for thermal damage was estimated to be 59-61 degrees C when samples were heated for 10 min, 62-63 degrees C when heated for 1 min, and 66-67 degrees C when heated for 10 sec; the threshold exposure time at 60 degrees C was estimated to be 7-12 min. These results indicate a temperature of 60 degrees C for 1 min is well tolerated by human donor sclera; information of in vivo studies is required to validate whether this setting can be used in transscleral thermotherapy (TSTT) for choroidal melanoma.

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.

Effects of transpupillary thermotherapy on immunological parameters and apoptosis in a case of primary uveal melanoma.

Transpupillary thermotherapy (TTT) is a new treatment modality for uveal melanoma. We studied whether application of TTT influences the immunogenicity of the tumour cells in vivo or the expression of molecules related to apoptosis. Immunohistochemistry using monoclonal antibodies directed against HLA molecules, HMB45, P53, Fas ligand (FasL), Fas, Bcl-2 and tumour-infiltrating cells was applied to sections of an enucleated eye containing a uveal melanoma that received TTT 1 week before enucleation. The innermost part of the tumour which had been exposed directly to the laser treatment showed no staining for HLA antigens, nor for Fas or FasL epitopes. The intermediate part of the tumour showed a wet necrosis and HLA expression similar to the expression in the peripheral tumour. A large number of macrophages were observed in the necrotic as well as the intact tumour tissue, especially bordering the wet necrotic area. FasL and Bcl-2 were only expressed in the viable, outer part of the tumour. This immunological evaluation of one case of uveal melanoma treated with TTT revealed that TTT may not only have a direct destructive effect on the primary tumour, but may also influence the immunogenicity of uveal melanoma cells, induce infiltration of macrophages into the tumour, and induce apoptosis. The presence of many macrophages suggests that they play a role in the removal of the TTT-treated tumour tissue by phagocytosis.