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Objective: Fetal infection with human parvovirus B19 (hParvo-B19) has been associated mainly with fetal anemia, although data regarding other fetal hematologic effects are limited. Our aim was to assess the rate and consequences of severe fetal thrombocytopenia after fetal hParvo-B19 infection., Study Design: We conducted a retrospective study of pregnancies that were complicated by fetal hParvo-B19 infection that underwent fetal blood sampling (FBS). The characteristics and outcomes of fetuses with severe thrombocytopenia (<50 × 10(9)/L) were compared with those of fetuses with a platelet concentration of ≥50 × 10(9)/L (control fetuses). Fetuses in whom 3 FBSs were performed (n = 4) were analyzed to assess the natural history of platelet levels after fetal hParvo-B19 infection., Results: A total of 37 pregnancies that were affected by fetal hParvo-B19 infection were identified. Of the 29 cases that underwent FBS and had information regarding fetal platelets, 11 cases (38%) were complicated by severe fetal thrombocytopenia. Severely thrombocytopenic fetuses were characterized by a lower hemoglobin concentration (2.6 ± 0.9 g/dL vs 5.5 ± 3.6 g/dL; P = .01), lower reticulocyte count (9.1% ± 2.8% vs 17.3% ± 10.6%; P = .02), and lower gestational age at the time of diagnosis (21.4 ± 3.1 wk vs 23.6 ± 2.2 wk; P = .03). Both the fetal death rate within 48 hours of FBS (27.3% vs 0%; P = .02) and the risk of prematurity (100.0% vs 13.3%; P < .001) were higher in fetuses with severe thrombocytopenia. Fetal thrombocytopenia was more common during the second trimester but, in some cases, persisted into the third trimester. Intrauterine transfusion (IUT) of red blood cells resulted in a further mean decrease of 40.1% ± 31.0% in fetal platelet concentration., Conclusion: Severe fetal thrombocytopenia is relatively common after fetal hParvo-B19 infection, can be further worsened by IUT, and may be associated with an increased risk of procedure-related fetal loss after either FBS or IUT., (Copyright © 2015. Published by Elsevier Inc.)

Both "early" (< 16 weeks' gestation) and "late" (> 26 weeks' gestation) presentations of twin-twin transfusion syndrome (TTTS) are rare and challenging complications of monochorionic/diamniotic twin pregnancies. Growing evidence suggests that fetoscopic laser therapy for both "early" and "late" TTTS is feasible, safe, and yields similar outcomes to cases treated between 16 and 26 weeks' gestation. We suggest reevaluation of conventional gestational age guidelines for laser therapy for TTTS., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Pregnancy is rare in women with ESRD and when it occurs, it is often accompanied by significant maternal and fetal morbidity and even mortality. Preliminary data from the Toronto Nocturnal Hemodialysis Program suggested that increased clearance of uremic toxins by intensified hemodialysis improves pregnancy outcomes, but small numbers and the absence of a comparator group limited widespread applicability of these findings. We compared pregnancy outcomes from 22 pregnancies in the Toronto Pregnancy and Kidney Disease Clinic and Registry (2000-2013) with outcomes from 70 pregnancies in the American Registry for Pregnancy in Dialysis Patients (1990-2011). The primary outcome was the live birth rate and secondary outcomes included gestational age and birth weight. The live birth rate in the Canadian cohort (86.4%) was significantly higher than the rate in the American cohort (61.4%; P=0.03). Among patients with established ESRD, the median duration of pregnancy in the more intensively dialyzed Toronto cohort was 36 weeks (interquartile range, 32-37) compared with 27 weeks (interquartile range, 21-35) in the American cohort (P=0.002). Furthermore, a dose response between dialysis intensity and pregnancy outcomes emerged, with live birth rates of 48% in women dialyzed ≤20 hours per week and 85% in women dialyzed >36 hours per week (P=0.02), with a longer gestational age and greater infant birth weight for women dialyzed more intensively. Pregnancy complications were few and manageable. We conclude that pregnancy may be safe and feasible in women with ESRD receiving intensive hemodialysis., (Copyright © 2014 by the American Society of Nephrology.)

Objective: The aims of this study were to review fetal and maternal outcomes after management of the compromised perinatal airway via operation on placental support or ex utero intrapartum treatment and to discuss implications for future management of these complex and rare cases., Methods: We have presented a retrospective case series of 12 neonates requiring airway management on placental support at a single tertiary care, academic center., Results: One mother experienced significant blood loss. Operative recovery times were unremarkable. Eight neonates required airway management due to mass obstruction, two for removal of an endotracheal balloon for fetoscopic treatment of congenital diaphragmatic hernia, one for laryngeal atresia, and one for severe retrognathia. One of our series is an unusual case of management on placental support after vaginal delivery. Another child would have ideally been managed on placental support, but an extremely short umbilical cord prevented this. Even though the airway was secured in all 12 cases, five neonates died in the perinatal period., Conclusions: These procedures have a risk for substantial maternal blood loss. Despite excellent rates of success securing the neonatal airway, children who require management on placental support still have high mortality. A formalized multidisciplinary approach at our institution has enhanced preparedness for these cases., (© 2013 John Wiley & Sons, Ltd.)

Background: Pregnancy in a rudimentary uterine horn is a rare form of ectopic pregnancy with a high risk of rupture. Management usually involves excision of the rudimentary horn. If diagnosed after the first trimester, it has been managed in the past by laparotomy., Case: A primigravid woman was found on routine ultrasound to have a rudimentary horn pregnancy. The diagnosis was confirmed on MRI, and a thin uterine wall was demonstrated. Management comprised fetal injection of potassium chloride followed by complete laparoscopic excision of the rudimentary horn at 16 weeks' gestation., Conclusion: Laparoscopic management of a mid-trimester rudimentary horn pregnancy is feasible, but expert radiological characterization is required for optimal surgical planning.

Pregnancy in patients with ESRD is rare and remains especially challenging. Because endocrine abnormalities and sexual dysfunction decrease fertility, conception rates have been remarkably low in this patient population. Moreover, when pregnancy does occur, hypertension, preeclampsia, anemia, intrauterine growth restriction, preterm delivery, stillbirth, and other complications can decrease the rate of a successful outcome. However, recent experiences with intensive hemodialysis managed by a multidisciplinary team are encouraging with respect to better overall outcomes for mothers and infants. In this article, we discuss the main causes of decreased fertility in dialysis-dependent women, review outcomes and complications of pregnancy among dialysis patients with a special focus on recent intensive hemodialysis data, and summarize the current best strategy to manage pregnant women on dialysis., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to compare perinatal outcomes of pregnancies that undergo "early" (<17 weeks' gestation) or "late" (>26 weeks' gestation) fetoscopic laser ablation of placental vascular anastomoses for twin-twin transfusion syndrome (TTTS) with "conventional" cases that were treated at 17-26 weeks' gestation., Study Design: We conducted a single center, retrospective analysis of 325 consecutive pregnancies that underwent fetoscopic laser therapy for severe TTTS., Results: Twenty-four "early," 18 "late," and 283 "conventional" pregnancies with severe TTTS underwent laser therapy. Fetoscopy duration, gestation at delivery, survival rate, and complications were comparable among groups, except for preterm premature rupture of membranes at <7 days after laser therapy, which was more common in the "early" group than in either of the other 2 groups., Conclusion: Laser therapy for TTTS at <17 or >26 weeks' gestation has similar outcomes to procedures done at 17-26 weeks' gestation. We suggest that conventional gestational age guidelines of 16-26 weeks for laser therapy for TTTS should be reevaluated., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: Women with spinal cord lesions present special challenges during pregnancy. We studied their pregnancy outcomes with regard to medical, obstetrical, and social concerns., Methods: We reviewed the records of pregnant women with spinal cord injury who attended our institution between 1999 and 2009., Results: Thirty-two women with a total of 37 pregnancies were identified. Most were nulliparous (65%) with either thoracic or lumbar spinal cord lesions due to neural tube defects (69%), trauma (19%), tumours (9%), or iatrogenic injury (3%). Most had undergone orthopedic surgery (63%) or neurosurgery (53%). The most common medical conditions were neurogenic bladder (53%), anemia (16%), autonomic hyperreflexia (9%), and elevated BMI > 30 (6%). Recurrent urinary tract infection occurred in 32%. Antibiotic suppression against bacteriuria was used in 35%. Antenatal hospitalization occurred in 46%, most often because of threatened preterm labour (19%). There were 33 live births and two stillbirths (6%). Preterm birth < 37 weeks occurred in 24%. Vaginal birth occurred in 33%., Conclusion: Pregnant women with spinal cord lesions generally have successful pregnancy outcomes. However, their pregnancies are at significant risk for preterm birth, infection, and Caesarean section. Coordinated multidisciplinary care is recommended for optimal management of these pregnancies.

The ovulatory menstrual cycle is known to be affected on multiple levels in women with advanced renal disease. Menstrual irregularities, sexual dysfunction, and infertility worsen in parallel with the renal disease. Pregnancy in women with ESRD on dialysis is therefore uncommon. Furthermore, when pregnancy does occur, it can prove hazardous to both mother and baby owing to a multitude of potential complications including accelerated hypertension and preeclampsia, poor fetal growth, anemia, and polyhydramnios. Data are emerging, however, to suggest that pregnancy while on intensified renal replacement regimens may result in better pregnancy outcomes, and emerging trends include the decreased rate of therapeutic abortions probably reflecting a change in counseling practices over time. Nevertheless, a pregnant woman on intensive dialysis requires meticulous follow-up by a dedicated team including nephrology, obstetrics, and a full multidisciplinary staff. In this article, we will address fertility issues in young women with ESRD, review pregnancy outcomes in women on both hemodialysis and peritoneal dialysis, and provide suggestions for the management of the pregnant women on intensive hemodialysis., (© 2011 Wiley Periodicals, Inc.)

Complicating up to 8% of pregnancies, preeclampsia is, in fact, the most common glomerular disease worldwide. In this article, we review the effect of normal pregnancy on the kidney as well as the role of the kidney in preeclampsia. We discuss blood pressure in pregnancy and preeclampsia, followed by the physiology of hyperfiltration in normal pregnancy as well as the pathophysiology of hypofiltration and proteinuria in preeclampsia. Recent studies have suggested that the clinical syndrome of preeclampsia, which recovers rapidly after delivery of the placenta, is caused by impaired vascular endothelial growth factor signaling that disturbs the status of vascular dilatation as well as the symbiosis between the glomerular endothelium and the podocytes. Finally, we discuss the intriguing association between chronic kidney disease (CKD) and preeclampsia. We hypothesize that the imbalance between angiogenic and anti-angiogenic factors, which may be common to both preeclampsia and CKD, might explain why CKD predisposes pregnant women to develop preeclampsia., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: An otherwise healthy 31-year-old gravida 2 para 1 woman with a spontaneous dichorionic, diamniotic twin pregnancy presented with hypertension, nephrotic syndrome and renal insufficiency at 19 weeks' gestation. Fetal ultrasound revealed severe intrauterine growth restriction of one fetus and measurement of serum anti-angiogenic and angiogenic factors were consistent with a profound anti-angiogenic state. After one fetus died and the placenta became increasingly echogenic, the patient improved clinically, and weekly ultrasound assessments of the intact co-twin from 22 weeks onwards demonstrated symmetrical fetal growth along the 10th centile. Repeat serum angiogenic factors at 24 weeks' gestation revealed considerable improvement of the anti-angiogenic state and paralleled resolution of the clinical syndrome., Investigations: Physical examination, laboratory evaluations including full blood count, liver function tests, electrolytes, renal function tests, screening for glomerular-based disease, 24-h urine collection for total protein, analysis of serum anti-angiogenic and angiogenic factors, fetal ultrasonography and placental Doppler examination., Diagnosis: Spontaneous resolution of early-onset pre-eclampsia after single fetal demise in a twin pregnancy., Management: Labetalol was given to treat hypertension and furosemide was given as needed for edema. The patient was closely followed up throughout pregnancy in a combined nephrology/obstetrics outpatient clinic.

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.

The congenital myasthenia syndromes form a heterogeneous group of genetic diseases characterized by defective neuromuscular transmission. Although they have muscle fatigability in common with the acquired immune myasthenia syndrome, there are important pathophysiological, diagnostic, management and progression pattern differences between them. We report the management of a 28-yr-old patient with longstanding congenital myasthenia syndromes, who underwent an elective cesarean delivery under spinal anesthesia. Muscle imbalance plus weakness-related scoliosis and chronic respiratory failure complicated her management. Ultrasonography was used to facilitate the spinal anesthetic. Intraoperative noninvasive positive pressure ventilation maintained lung volumes effectively and prevented deterioration in respiratory function.

Background and Objectives: Women of childbearing age on conventional hemodialysis (CHD) have decreased fertility when compared with the general population. Even in women who conceived, maternal morbidity and fetal mortality remained elevated. We hypothesized that nocturnal hemodialysis (NHD) (3 to 6 sessions per week, 6 to 8 h per treatment), by augmenting uremic clearance, leads to a more hospitable maternal environment and therefore superior outcomes in fertility and pregnancy compared with CHD., Design, Setting, Participants, and Measurements: This is a descriptive cohort study of all female patients achieving pregnancy and delivering a live infant while on NHD at the University Health Network, St. Michael's Hospital, and Humber River Regional Hospital from 2001 to 2006 in Toronto, Canada. Our primary objective was to describe maternal and fetal outcomes in addition to the changes in biochemical parameters after conception in our cohort., Results: Our cohort included five patients (age range, 31 to 37 yr) who had seven pregnancies while on NHD and delivered six live infants. All had previously been on CHD, but none conceived during that time. In all patients, the amount of hemodialysis was increased (from a weekly mean of 36 +/- 10 to 48 +/- 5 h; P < 0.01) after pregnancy was diagnosed. Mean predialysis blood urea and mean arterial BP were maintained within normal physiological parameters. The mean gestational age of the cohort was 36.2 +/- 3 wk and the mean birth weight was 2417.5 +/- 657 g. The maternal and fetal complications observed in the cohort included intrauterine growth restriction or small for gestational age (n = 2), preterm delivery (<32 wk) (n = 1), and shortened cervix threatened labor (n = 1). Anemia was accentuated during pregnancy, and intravenous iron and erythropoietin requirements were increased. To maintain normal physiological indices for plasma phosphate, an augmented dialysate phosphate supplementation regimen was required., Conclusions: NHD may allow for improved fertility. Delivering a live infant at a mature gestational age is feasible for patients on NHD. Our cohort tended to have fewer maternal and fetal complications compared with historical controls. Hemoglobin and phosphate levels must be monitored with treatment adjusted accordingly.

Purpose: Bone morphogenetic protein-7 (BMP7), a member of the TGF-beta superfamily, is essential for early ocular morphogenesis, and lack of BMP7 causes epithelial development disturbances in the eye. In the present study, the association of tumorigenicity and malignant behavior of human uveal melanoma with BMP7 expression and the possibility that overexpression of BMP7 in uveal melanoma affects intraocular tumor growth in vivo were investigated., Methods: To establish the role of BMP7 in uveal melanoma progression, the human OCM-1 cell line was stably transfected to overexpress BMP7 (OCM-1 FRT/BMP7) using targeted homologous recombination., Results: Transcriptional profiling revealed low or no detectable expression of BMP7 in primary tumor tissue of patients with uveal melanoma. In line with these clinical observations, BMP7 mRNA levels were low or not detectable in cultured human uveal melanoma cell lines, when compared with normal cultured melanocytes. Inoculation of OCM-1 FRT/BMP7 cells into the anterior chamber of the eye of nude mice inhibited tumor progression significantly, compared with progression in the control cell line (no BMP7 expression)., Conclusions: Collectively, the data provide novel evidence that decreased BMP7 expression contributes to progression of uveal melanoma. Furthermore, BMP7 may represent a novel therapeutic molecule for repression of tumor growth in uveal melanoma.

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., (Copyright (c) 2007 S. Karger AG, Basel.)

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.

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.

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.

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.

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.

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.

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.

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.

If laser pointers are powerful enough (> 5 mW), they can cause ocular damage. Most laser pointers in use, however, have low power, viz. 1 mW. In the peer-reviewed scientific literature worldwide not a single case of eye damage due to laser pointers is described. A review among Dutch ophthalmologists up to June 1998 revealed no cases of permanent damage caused by laser pointers. In view of the widespread use of laser pointers, the risk of retinal damage must be minimal, even with the types now banned. Laser pointers of 1 mW emitting light red or green light have sufficient visibility on projection screens. It is advisable to prohibit the sale of more powerful pointers to prevent excesses.

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.

We studied the effect of transpupillary thermotherapy (TTT) by a diode laser at 810 nm combined with episcleral ruthenium-106 plaque treatment (106Ru) on lens transparency in patients with choroidal melanoma. Lens transmission of blue-green light was measured by fluorophotometry in 17 patients treated with 106Ru treatment and TTT (measured 0.36 years after treatment), 12 patients treated with 106Ru alone (measured 19 years after treatment) and 25 age-matched healthy controls. Differences in lens transmission were not significant between treated and untreated fellow eyes (p > 0.15) nor between patient and control eyes (p > 0.25). TTT of choroidal melanoma combined with 106Ru plaque irradiation did not have a significant effect on the lens transparency up to 6 years after treatment.

This study was undertaken to assess long term changes in the lenticular autofluorescence and transmittance of healthy volunteers. Both eyes of 15 healthy volunteers aged 8 to 62 years were examined by slit-lamp examination and fluorophotometric measurements of lenticular autofluorescence (lambdaexc=415 nm-490 nm, lambdaem= 510 nm-550 nm) and transmittance (lambda=415 nm-550 nm) in 1983 and 1996. The changes in lenticular autofluorescence and transmittance between 1983 and 1996 were determined and compared with those calculated on the basis of age-dependence curves of a group of 56 healthy volunteers measured in 1983. These curves were obtained by approximation of the values of the 56 healthy volunteers by a linear, polynomial or exponential function of age, respectively. A mean yearly increase of lenticular autofluorescence of 8.69 ng . equivalent fluorescein . ml-1 . year-1 was observed in the 15 volunteers between 1983 and 1996 and this increase was significantly larger than that calculated on the basis of the three age-dependence curves in 1983 (6.36, 6.47 and 6.53 ng . equivalent fluorescein . ml-1 . year-1, P=0.0026, 0.0037 and 0.0044, respectively). The transmittance showed a mean yearly decrease of 0.508% . year-1 which was significantly larger than calculated on the basis of the three age-dependence curves in 1983 (0.153, 0.220 and 0.183% . year-1, P=0. 0033, 0.012 and 0.0059, respectively). One volunteer, i.e. the individual with the highest lenticular autofluorescence and lowest transmittance in 1983, had developed cataract in 1996. These measurements demonstrate for the first time, quantitative changes in lenticular autofluorescence and transmittance in a long term follow up. The at least 35% larger increase of autofluorescence and 130% larger decrease in transmittance in the follow-up group between 1983 and 1996 in comparison with the values based on age-dependent curves in 1983 could be caused by the increased solar UV radiation in The Netherlands during that period of time., (Copyright 1998 Academic Press Limited.)

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.

Over 100 new cases of uveal melanoma are diagnosed annually in the Netherlands. In the absence of metastases, eye-preserving treatment is possible in principle. Since 1984, Dutch patients are referred for eye-preserving treatment to Leiden University Hospital which consequently has gained great experience. Brachytherapy (with Ruthenium-106 applicators) is only suitable for uveal melanomas with a diameter < or = 15 mm and a prominence (thickness perpendicular to the sclera) < or = 5 mm; after 10 years, the eye was preserved in 80% of the patients; 75% retained a visual acuity > or = 0.25. Proton irradiation is being applied for large, strongly prominent melanomas in patients for whom enucleation is not acceptable, for instance with a melanoma in the only eye still functioning. The eyes could be preserved in 83.3% over a period of 5 years. Transpupillary thermotherapy combined with episcleral Ruthenium-106 application is called sandwich therapy; in a study involving 50 patients, 49 melanomas (98%) began to regress within 4 weeks and after a follow-up period of 12 months all tumours with a prominence < 5 mm had regressed completely.

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.

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.

Purpose: To examine the foveal cone photopigment kinetics in two patients with commotio retinae of the posterior pole (Berlin edema)., Methods: A noninvasive technique, called fundus reflection densitometry, was used to provide a measure of the amount of visual photopigment at the foveal area and the time constant of photopigment regeneration., Results: Strongly impaired foveal cone photopigment kinetics were found in two patients during the acute stage of commotio retinae. Complete recovery occurred within 3 months in both patients., Conclusion: Retinal opacification in Berlin edema is accompanied by a traumatic lesion at the level of the photoreceptor-retinal pigment epithelium (RPE) complex. These results support recent histopathologic data on commotio retinae, which revealed moderate photoreceptor outer segment disruption and retinal pigment epithelium damage. According to our data, such damage might be reversible.

Two patients, males of 31 and 15 years old, developed blunt injury of one eye, including hyphaema, due to a champagne cork. In one patient surgical evacuation was performed, the other recovered with drug therapy only. Inquiries in other ophthalmic departments in the Netherlands indicate that this type of trauma seems to be more frequent at the turn of the year.

Purpose: Fundus reflection densitometry was used as an objective means for monitoring the recovery of foveal cone photopigments in nine patients who underwent anatomically successful surgery of a rhegmatogenous retinal detachment with macular involvement., Methods: Postoperative assessment of foveal densitometry, visual acuity, color matching, and the Amsler grid were performed at repeated intervals for up to 14 months., Results: Gradual recovery of foveal cone photopigments was found in all patients 1 to 14 months after surgery, with considerable interindividual variation. Maximal recovery to values equalling those in the fellow eye was found in only one patient with a macular detachment duration of 5 days. All other patients had final photopigment densities below those of the fellow eye. The length of the preoperative detachment period was inversely related to the recovery of photopigment. The recovery of photopigment seems to increase further in the second year after surgery. Visual acuity increased rapidly in all patients during the first 6 months after surgery, to levels ranging between 20/67 and 20/25; thereafter, visual acuity did not change. A return to normal color matching after an episode of pseudoprotanomaly was found in four of nine patients, whereas pseudoprotanomaly remained in five patients. Complete resolution of metamorphopsia after surgery was seen only in the patient who had the shortest detachment duration. Metamorphopsia was consistent with decreased foveal cone photopigment densities., Conclusion: Foveal densitometry shows a slow recovery of the cone photopigments after reattachment, probably because of regrowth and realignment of the cone photoreceptor outer segments and metabolic recovery of the retinal pigment epithelium-cone photoreceptor complex. Recovery of photopigment, color matching, and metamorphosia follow a slower time course than recovery of visual acuity.

In retinitis pigmentosa patients the effect of cystoid macular edema on colour vision was studied. The occurrence of cystoid macular edema decreases with increasing colour vision defect. The mutual proportion of the main types of colour vision defects remains stable until visual acuity has dropped to 0.5; at lower VA levels the number of red-green defects increases. Neither the finding of a blue-yellow colour vision defect in FM100 Hue testing nor the appearance of anomaloscopic pseudoprotanomaly is influenced by cystoid macular edema. The authors conclude that cystoid macular edema in retinitis pigmentosa patients mainly affects visual acuity and not colour vision. They also noted a familial occurrence of cystoid macular edema.

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.

A 28-year-old man with multiple evanescent white dot syndrome (MEWDS) in the left eye was examined with a scanning laser densitometer. The first measurements were taken in the acute stage, and repeat examinations were performed during the process of recovery. Fundus pictures were obtained from a 20 degrees retinal field, in dark and light adapted stages. From these images visual pigment density maps were derived. In the acute stage of the disease, maps revealed small round areas of absent visual pigment, which did not always correspond with the visible white dots. The areas of absent visual pigment density were also larger than the white dots seen on funduscopic examination. Single spot densitometry at the fovea was also performed and showed no significant density difference of the foveal cones. Rod density difference measured at a locus 16 degrees in the temporal retina was much lower than normal with an increased time constant of rhodopsin regeneration. Ten weeks after the onset of the disease, no white dot lesions were visible on funduscopic examination. Rod density difference and regeneration time had become normal again, but with scanning laser densitometry the abnormal areas of no pigment were still faintly visible. It is concluded that these findings, completed with data of electroretinography, anomaloscopic testing, and perimetry, are in agreement with a metabolic disturbance at the level of the retinal pigment epithelium-photoreceptor complex.

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.

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.

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.

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.

A 26-year-old man with sex-linked juvenile central and peripheral retinoschisis showed on fluorescein angiography an avascular lower temporal periphery, bordered at the central side by abnormal capillaries in a dendrite-like structure. In dominant exudative vitreoretinopathy an identical picture without schisis can be seen in the periphery. This feature seems to be a rare phenomenon in sex-linked juvenile retinoschisis. However, routine peripheral ophthalmoscopy and fluorescein angiography (especially inferotemporal) may reveal more cases.

Rod densities were measured in ten patients with congenital stationary night blindness (CSNB) using the Utrecht densitometer. In five patients rod density was within the range observed in a group of control subjects. One of these patients reached a normal rod two-way density after a prolonged regeneration time. In five patients with different hereditary patterns of CSNB we found decreased amounts of rhodopsin. These observations deviate from the findings on four CSNB patients hitherto described in the literature, where normal concentrations and kinetics of rhodopsin were found. We observed no relationship between the age of CSNB patients and mode of rhodopsin kinetics. No inconsistencies between rod densitometry and electro-retinography were revealed. The different electroretinography patterns were not helpful in predicting the densitometric responses in CSNB. The present results included, five of fourteen CSNB patients ever studied with the technique of retinal densitometry show abnormal rhodopsin kinetics. We propose a schema of CSNB subtyping based on the different rhodopsin kinetics.