[Economic Short-Term Cost Model for Stereotactic Radiotherapy of Neovascular AMD]. / Ökonomisches Kostenmodell zur Radiotherapie der neovaskulären AMD.

OBJECTIVES: Stereotactic radiation therapy (Oraya, OT) is available as a second line therapy for patients who, despite intensive anti-VEGF therapy for neovascular AMD, do not show an improvement in CNV. As OT is expensive (5,308 €), the short term economics for starting this therapy were investigated. METHODS: A short-term cost model was set up in MS Excel with a two year time horizon. On the basis of the data of the randomised, controlled INTREPID pivotal trial and current treatment practice in Germany, the costs were compared of conventional anti-VEGF therapy, with or without a single OT treatment. Patients with an active lesion after initial anti-VEGF therapy and a maximum lesion diameter ≤ 4 mm were included. Modeled cost components/aspects were direct savings from injection number, control follow-up examinations and aids, as well as anti-VEGF switches. Costs for Germany were employed and a univariate sensitivity analysis was performed to address the existing uncertainty. RESULTS: For the patients with a maximum AMD lesion diameter ≤ 4 mm and a macula volume > 7.4 mm(3), the INTREPID trial showed a mean reduction of 3.68 intravitreal injections for 16 Gy radiation versus sham over a time period of 2 years. These 3.68 IVM result in ~ 4,500 € direct cost savings. Moreover, due to the higher response rate with 16 Gy radiation, the number of follow-up visits and aids can be reduced, which results in savings between 207 € and 1,224 € over 2 years. After radiation, fewer anti-VEGF switches for low or non-responders are expected, which is modeled to result in ~ 1.7 fewer injections over 2 years. Due to overall fewer injections, fewer endophthalmitis cases would be expected. However, endophthalmitis and microvascular abnormalities, which can be observed in a few cases, are associated with low or non-quantifiable costs in this cost-cost comparison model. In summary, cost reductions of between 6,400 and 8,500 € are predicted in the model over two years, which have to be compared to the costs of a single application of OT. CONCLUSIONS: The short-term economic analysis shows that anti-VEGF therapy combined with OT results in savings above the costs for OT itself over a 2 year time horizon. Overall, the approach gives potential cost reductions, if the appropriate indication is followed.

[Functional and morphological correlations in macular hole surgery]. / Funktionelle und morphologische Korrelationen in der Makulaforamen-Chirurgie.

BACKGROUND: The purpose of this study is to establish the correlation between functional and morphological aspects before and 12 months after macular hole surgery. METHODS: In this prospective, interventional, consecutive study 16 eyes of 16 patients were included. All eyes received a successful transconjunctival 23-gauge vitrectomy with ILM peeling after initial diagnosis and maximum duration of symptoms of two months. Preoperatively and 3, 6 and 12 months postoperatively determinations of best-corrected visual acuity (logMAR), a 10° microperimetry (MP-1) and a spectral-domain based optical coherence tomography (SD-OCT) examination were performed. The photoreceptor layer (inner and outer segment, IS/OS) was evaluated based on SD-OCT images and correlated with data assessed by microperimetry analysis in the foveal and parafoveal region. RESULTS: After three months a stabilisation of BCVA with regeneration of the IS/OS line, an improvement of the fixation behaviour and the macular sensitivity could be observed. A significant restitution of the IS/OS line was observed after 12 months. Best corrected visual acuity, mean overall macular sensitivity and fixation improved significantly within the twelve month observation period (p < 0.05). Comparison of patients with at least two lines of visual acuity gain with patients having less than two lines of visual acuity gain 12 months after surgery showed no statistically significant difference in regeneration of the IS/OS integrity in the fovea (p = 0.433), but a difference was seen in the parafoveal region. A postoperative visual acuity gain of at least two lines was significantly more often seen in eyes with postoperative continuous IS/OS line in the parafoveal sectors compared to eyes with persistent IS/OS defects (p < 0.02). CONCLUSION: Correlations of morphological and functional improvements can be observed after successful micro-invasive macular hole surgery. The extent of the preoperative IS/OS defect, particularly in the parafoveal region, is a good predictive parameter for the postoperatively obtained macular sensitivity. The prediction of the postoperative visual acuity should not be made on the basis of a single clinical, anatomic finding.

Budget impact of the Oncotype DX® test compared to other gene expression tests in patients with early breast cancer in Germany.

PURPOSE: Gene expression tests can inform decisions on whether to recommend chemotherapy for patients with HR+, HER2- early breast cancer. The goal of this analysis was to compare treatment costs by an expanded budget impact model of reimbursed gene expression tests in Germany. METHODS: A cost comparison was constructed as an expanded budget impact model to calculate average total costs per patient covered by public health insurance. Based on the strong clinical evidence from the prospective randomized controlled trial TAILORx including more than 10,000 patients with HR+ and node negative breast cancer, the assumption was made that the Oncotype DX® test accurately predicts chemotherapy benefit and clinical outcomes. For the further reimbursed tests (EndoPredict®, MammaPrint®, Prosigna®), results from comparative studies - aligned with prognosis studies - as analyzed in IQWiG Rapid Report D19-01 were applied. RESULTS: The use of the Oncotype DX test led to estimated average savings per patient of 2,500 € vs. EndoPredict, 1,936 € vs. MammaPrint, and 649 € vs. Prosigna. Savings were achieved by reduction of unnecessary chemotherapy use, a consequence of false-positive test results (EndoPredict 73%, MammaPrint 42%, Prosigna 20%). False-negative test results (EndoPredict 5%, MammaPrint 22%, Prosigna 49%) reduced necessary chemotherapies, which initially results in cost savings, but may lead to increased long-term costs associated with management of progressive disease. CONCLUSION: The results from this model suggest that the use of the Oncotype DX test reduces the cost of health care in Germany making it the most cost effective test compared to the further tests.

[Static retinal vessel analysis in acute blood pressure increase]. / Statische retinale Gefäßanalyse bei akutem Blutdruckanstieg.

BACKGROUND: The aim of this study was to examine the changes in static analysis of the retinal vasculature during an acute rise of blood pressure in young normal subjects. MATERIAL AND METHODS: An increase of blood pressure was induced in 30 young normal subjects (age 18 - 30 years) by physiological stress. Retinal fundus photographs were taken before and immediately after the stress. The central retinal artery equivalent (CRAE), the central retinal vein equivalent (CRVE) and the arterio-venous ratio (AVR) were calculated by automated vessel analysis software (Talia Technology, Lod, Israel). The same vessel segments were measured before and after the rise of blood pressure. RESULTS: At rest, mean CRAE was 97.3 ± 9.6 micrometer, CRVE 114.5 ± 12.5 micrometer and AVR 0.85 ± 0.08. The mean systemic perfusion pressure was elevated by physiological stress from a mean of 90.7 ± 7 mmHg by 18.0 ± 7.8 mmHg. The static retinal vessel analysis showed a constriction of the arteries by a mean of -1.3 ± 3.9 microns and a venous dilatation of 0.6 ± 7.2 microns. The retinal AVR was diminished significantly (p = 0.02) by -0.015 ± 0.032. The degree of arterial constriction - but not the change of AVR - correlated significantly (r = -0.39; p = 0.048) with the degree of rise of blood pressure. CONCLUSION: Retinal autoregulation during acute increase of blood pressure in young normal subjects can be measured by static retinal vessel analysis.

[The role of light in the developement of RPE degeneration in AMD and potential cytoprotection of minocycline]. / Altersbedingte Makuladegeneration: die Rolle von Licht bei der Entstehung degenerativer Veränderungen im menschlichen RPE und möglicher Zell-Schutz durch Minocyclin.

BACKGROUND: Light-induced oxidative stress is an suggested reason for retinal pigment epithelium (RPE) degeneration in age-related macular degeneration (AMD). This study investigates the influence of light on intracellular reactive oxygen species (ROS) and apoptosis in the human RPE and potential cytoprotective effects of the tetracycline antibiotic minocycline. METHODS: Primary human RPE cells were either pre- or post-incubated with minocycline and then exposed to white light or oxidative stress (600 µM, H(2)O(2)). Then viability, induction of intracellular reactive oxygen species (ROS), apoptosis and cell death was determined. Expression of apoptotic BAX and anti-apoptotic Bcl-2 protein and their mRNA were determined by RT-PCR and Western blot analysis. RESULTS: Both light exposure and oxidative stress decreased RPE cell viability and Bcl-2 expression and increased intracellular ROS, apoptotic cell death, and BAX expression. Minocycline reduced these effects under certain conditions. CONCLUSIONS: This study demonstrates that minocycline effectively protects human RPE cells against oxidative damage. However, in the light of minocycline's photosensitising properties its potential role in AMD treatment needs further evaluation.

Sorafenib protects human optic nerve head astrocytes from light-induced overexpression of vascular endothelial growth factor, platelet-derived growth factor, and placenta growth factor.

OBJECTIVES: Growth factors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and placenta growth factor (PlGF) are key players in the development of diabetic retinopathy, age-related macular degeneration, and other retinal neovascular diseases. Glial cells provide a significant source of retinal growth factor production under physiologic and pathologic conditions. Cumulative light exposure has been linked to increased retinal growth factor expression. Previous reports indicate that sorafenib, an oral multikinase inhibitor, might have a beneficial effect on retinal neovascularization. This study was designed to investigate the effects of sorafenib on light-induced overexpression of growth factors in human retinal glial cells. METHODS: Primary human optic nerve head astrocytes (ONHAs) were exposed to white light and incubated with sorafenib. Viability, expression, and secretion of VEGF-A, PDGF-BB, and PlGF and their mRNA were determined by reverse transcription-polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. RESULTS: Light exposure decreased cell viability and increased VEGF-A, PDGF-BB, and PlGF expression and secretion. These light-induced effects were significantly reduced when cells were treated with sorafenib at a concentration of 1 microg/ml. CONCLUSION: Sorafenib significantly reduced light-induced overexpression of VEGF-A, PDGF-BB, and PlGF in primary human ONHAs. Sorafenib has promising properties as a potential supportive treatment for retinal neovascularization.

[Disinfecting contact tonometers - a systematic review]. / Desinfektion von Kontakt-Tonometern - ein systematischer Review.

OBJECTIVE: The aim of this study is to provide the best available evidence on how to disinfect contact Goldman tonometers. METHODS: A systematic review of all articles on disinfection of contact tonometers was conducted. Articles published up to July 2008 were identified in Medline, Embase and references from included articles. Two observers participated in the data retrieval and assessment of the studies identified. RESULTS: A total of 89 articles was retrieved, of which 58 could be included. Of those, 18 were clinical studies, 17 experimental microbiological studies, 8 expert assessments or guidelines and 15 reviews, surveys, descriptions of new methods. The clinical studies illustrate the importance of the problem, possible side effects of some disinfection methods but yield inconclusive results regarding efficacy. Experimental studies investigated a variety of bacterial and virological questions as well as material damage by disinfection. Both chlorine-based and hydrogen peroxide-based liquid disinfection were shown to be effective if applied for 5 min. Inconsistent results exist for alcohol wipes and UV disinfection - material damage has been described for both. The US guidelines and most expert recommendations are supported by evidence of the existing data. CONCLUSIONS: Chlorine-based and hydrogen peroxide-based liquid disinfections for 5 minutes are effective and relatively safe for disinfecting contact tonometers.

[Retinal pigment epithelial tears after intravitreal injection of bevacizumab for AMD. Frequency and progress]. / Retinale Pigmentepithelrisse nach intravitrealem Bevacizumab bei AMD. Häufigkeit und Verlauf.

PURPOSE: Intravitreal injection of the antibody bevacizumab is unofficially becoming more and more the "standard of care" in the treatment of neovascular AMD. After initial concerns about possible systemic adverse events of the drug, intravitreal injection has as yet shown a very good safety profile. Due to the common application of this VEGF inhibitor it is of great importance to report complications that may be related to the use of bevacizumab. In this scope we present a series of patients with predominantly serous detachment of the retinal pigment epithelium (PED), who developed a tear (rip) in the retinal pigment epithelium (RRPE) after intravitreal application of bevacizumab. METHODS: Our data are based on a prospective, consecutive, interventional case series of 420 patients with neovascular AMD. These patients received at least 1 intravitreal application of 1.25 mg bevacizumab within the period of 1 year. Follow-up examinations were every 4-6 weeks. Visits were documented with best corrected visual acuity according to the ETDRS standard, biomicroscopy of the retina, intraocular pressure measurement, evaluation of central retinal thickness, fluorescein angiography and fundus photography. RESULTS: Of 420 patients, 74 were classified as having predominantly serous PED. In the further course 13 out of 74 patients developed RRPE. Patients who had an intact subfoveal RPE, gained vision scores of 1.4+/-8.3 ETDRS letters (span width -15 to 14) despite RRPE or had stable Snellen vision of 0.0+/-0.1 logMar. In contrast patients with no subfoveal RPE due to RRPE showed loss of vision of -6.2+/-7.2 ETDRS letters (span width -15 to 1). CONCLUSION: This case series describes RRPE as a novel complication of intravitreal anti-VEGF therapy with bevacizumab. However, it seems that this complication is limited to the entity of predominantly serous PED. These patients should therefore be informed about the risk of RRPE before initiating anti-VEGF therapy with bevacizumab, although the reverse conclusion to generally exclude patients with PED from anti-VEGF therapy is not justifiable due to therapeutic efficiency and associated gain of vision.

[Bevacizumab is not toxic to human anterior- and posterior-segment cultured cells]. / Bevacizumab wirkt nicht toxisch auf Zellen des menschlichen Auge.

OBJECTIVE: Intravitreal anti-vascular endothelial growth factor (VEGF) treatment with bevacizumab (Avastin) has emerged as a promising therapy for the treatment of choroidal neovascularisation in age-related macular degeneration. Intravitreal administration of bevacizumab is "off-label," and only very limited data regarding short-term toxicity exist. Therefore, we investigated the safety of different doses of bevacizumab on the anterior- and posterior-segment cells of the human eye. METHODS: Primary human retinal pigment epithelium (RPE) cells, human optic nerve head astrocytes (ONHA), human trabecular meshwork cells (TMC), and cornea buttons not suitable for transplantation were treated with bevacizumab (25 microg/ml, 250 microg/ml, and 2,500 microg/ml) for 48 h, corresponding to 0.1x, 1x, and 10x the dosage used intravitreally. Bevacizumab-related toxicity was evaluated by a colorimetric test (MTT) measuring inhibition of RPE, ONHA, and TMC cell proliferation. Additionally, cell viability was quantified by live/dead fluorescence assay. Corneal endothelium was quantified by phase-contrast microscopy. RESULTS: Bevacizumab showed adverse effects on primary RPE cell proliferation as well as on cell viability at a concentration of 2,500 microg/ml. The lower concentrations of 25 microg/ml and 250 microg/ml had no influence on RPE cell proliferation or cell viability. There was no toxicity for any investigated concentration on human ONHA, TMC, or corneal endothelium. CONCLUSION: In this study, a 10-fold concentration (compared with common clinical use) of the VEGF-blocking antibody bevacizumab had toxic effects on primary RPE. There was no toxicity for lower concentrations or toxicity to other cell types of the anterior and posterior segments. Therefore, the clinical use of bevacizumab at concentrations of 1-1.25 mg intravitreally seems to be safe.

Cost utility for penetrating keratoplasty in patients with poor binocular vision.

PURPOSE: Cost-utility and cost-effectiveness analyses are of increasing importance to clinicians and health policy experts. This study determines the costs in Germany and other countries in relation to gain of utility for patients with bilateral poor vision owing to corneal disease undergoing penetrating keratoplasty (PK) in 1 eye. DESIGN: A cost-utility analysis was performed using retrospective clinical data and high-level evidence-based data. PARTICIPANTS: Sixty patients (mean age, 46.3 years) with bilateral poor vision who underwent PK for corneal disease. METHODS: Visual acuity and utility values were obtained before and 1 year after PK and after suture removal. A 10-year graft survival rate of 80% was assumed. Expenses included costs for the corneal transplant and surgery, medication, and optical rehabilitation. A discount rate of 5% was applied for costs and quality-adjusted life years (QALYs). Cost-utility analysis encompassed a 10-year period after surgery. MAIN OUTCOME MEASURES: The number of QALYs was calculated for the study group undergoing PK. This was divided into the cost of the procedure to get the number of euros spent per QALY gained. RESULTS: Median binocular preoperative visual acuity was -log mean angle of resolution (-logMAR) 0.91+/-0.53 (Snellen equivalent 20/160) yielding a utility value of 0.67. After suture removal and optical rehabilitation, binocular visual acuity increased to median -logMAR 0.36+/-0.36 (20/46) with a utility value of 0.79. Over the 10 years after surgery and considering graft survival and discounting, a cost utility of 9551 euros per QALY was gained (equivalent to US11,557 dollars). One-way sensitivity analysis yielded a range from 7706 euros to 12874 euros per QALY, highlighting the robustness of the model. CONCLUSIONS: Although an expensive procedure, PK is cost effective in patients with bilateral poor vision.

[Visual quality of life after vitreoretinal surgery for epiretinal membranes]. / Visuelle Lebensqualität nach vitreomakulärer Chirurgie bei epiretinalen Membranen.

PURPOSE: To date, the increase of visual acuity and morphological parameters have been used to assess the benefit of a surgical intervention. The aim of this prospective study was to evaluate changes in patients' visual quality of life due to vitreoretinal surgery for epiretinal membranes. PATIENTS AND METHODS: Twenty patients with unilateral epiretinal membrane and good visual acuity of the fellow eye were included. Best corrected visual acuity and visual quality of life assessed by the visual function index (VF-14) were obtained preoperatively and 3 months after pars plana vitrectomy and peeling. RESULTS: Median visual acuity increased from 0.28 to 0.4 postoperatively. Visual quality of life (VF-14 values) rose from 72.8+/-4.7 (SEM) to 83.3+/-2.9 (p<0.05). Analysis revealed that patients with preoperatively low VF-14 values and preoperatively low visual acuity notably profited from surgery. The increase of visual quality of life can be predicted better than increase of visual acuity. Combined cataract surgery had no significant influence. CONCLUSION: In addition to best corrected visual acuity, quality of life measurements are important predictive and outcome parameters to estimate the value of vitreoretinal surgery.

[Value-based medicine in ophthalmology]. / "Value-based medicine" in der Augenheilkunde.

PURPOSE: Value-based medicine (VBM) unifies costs and patient-perceived value (improvement in quality of life, length of life, or both) of an intervention. Value-based ophthalmology is of increasing importance for decisions in eye care. METHODS: The methods of VBM are explained and definitions for a specific terminology in this field are given. The cost-utility analysis as part of health care economic analyses is explained. RESULTS: VBM exceeds evidence-based medicine by incorporating parameters of cost and benefits from an ophthalmological intervention. The benefit of the intervention is defined as an increase or maintenance of visual quality of life and can be determined by utility analysis. The time trade-off method is valid and reliable for utility analysis. The resources expended for the value gained in VBM are measured with cost-utility analysis in terms of cost per quality-adjusted life years gained (euros/QALY). Numerous cost-utility analyses of different ophthalmological interventions have been published. CONCLUSION: The fundamental instrument of VBM is cost-utility analysis. The results in cost per QALY allow estimation of cost effectiveness of an ophthalmological intervention. Using the time trade-off method for utility analysis allows the comparison of ophthalmological cost-utility analyses with those of other medical interventions. VBM is important for individual medical decision making and for general health care.

[Screening for diabetic retinopathy and optic disc topography with the "retinal thickness analyzer" (RTA)]. / Screening der diabetischen Retinopathie und Papillentopographie mit dem "Retinal Thickness Analyzer" (RTA).

BACKGROUND: The RTA features a fundus photography mode and optic disc topography. Those two new modes were investigated regarding their clinical use. METHODS: First, the combination of wide-field photography with a retinal thickness map was assessed for tele-screening for diabetic retinopathy in 31 eyes. Second, normal values of the optic disc were collected on 30 non-glaucomatous probands in the non-mydriatic mode and compared to the results of the mydriatic mode, for which reproducibility was also investigated. RESULTS: For diabetic retinopathy, the RTA yielded mean 93% sensitivity for proliferative diabetic retinopathy and 100% sensitivity for detecting diabetic macular edema compared to clinical examination at specificities ranging from 58 to 96%. Regarding the measurements of the optic disc, the normal values in mydriasis coincided with those in miosis in all but 4 of 12 parameters. CONCLUSIONS: The RTA is suitable for application in tele-screening for diabetic retinopathy. The topography of the optic disc is highly reproducible and may be used for glaucoma diagnostics.

[Evaluation of portable TGDc-01 tonometers and comparison with the Goldmann applanation tonometer]. / Evaluation des mobilen TGDc-01-Tonometers und Vergleich mit dem Applanationstonometer nach Goldmann.

PURPOSE: The aim of this study was to evaluate patients' acceptance and intraocular pressure (IOP) readings of a new digital mobile tonometer (TGDc-01) and compare it to Goldmann applanation tonometry. METHOD: Measurements repeated five times with the TGDc-01 and three times with Goldmann tonometry were performed in 100 eyes of 100 patients by two independent investigators. Patients' acceptance of both techniques was evaluated by a visual analogue scale (VAS). RESULTS: The mean IOP with the TGDc-01 yielded 15.4 mmHg for investigator 1 and 12.7 mmHg for investigator 2 (range: 4-43 mmHg). Results of the measurements with Goldmann tonometry showed 17.6 mmHg for investigator 1 and 17.3 mmHg for investigator 2 (9-42 mmHg). The IOP difference of the two tonometry methods was highly significant (p<0.001). The intraobserver variability was 29% for investigator 1 and 8% for investigator 2. Mean IOP values of the two investigators taken with the TGDc-01 differed significantly (p<0.01) from each other by a mean of 2.6 mmHg. CONCLUSIONS: The new mobile tonometer TGDc-01 is better accepted by patients but IOP values are significantly lower compared to Goldmann tonometry and variability is high. Regarding glaucoma diagnostics it seems to be less suitable than Goldmann tonometry.

Interobserver and intraobserver variability of measurements of uveal melanomas using standardised echography.

AIMS: To report on the intraindividual and interindividual variability of tumour size (height and base diameter) measurements using standardised echography in a masked prospective study. METHODS: 20 consecutive eyes of 20 patients were examined on four different visits by three experienced examiners using standardised echography. As common in standardised echography, tumour height was evaluated with A-scan technique, while transverse and longitudinal base diameter were calculated with B-scan. RESULTS: Tumour height measurements using A-scan were more accurate than base diameter measurements using B-scan. The standard deviation for tumour height over all visits/measurements was 0.18 mm (A-scan), 0.79 mm for transverse, and 0.69 mm for longitudinal base diameters (B-scan). The interclass correlation coefficient (ICC) was much higher for tumour height measurements with A-scan (0.7735 for three examiners on one visit) than for transverse (0.6563) or longitudinal (0.4522) base diameter measurements with B-scan techniques. CONCLUSIONS: A-scan techniques for tumour height measurements provide very reproducible results with little intraindividual and interobserver variability. As B-scan techniques for tumour base evaluation are less accurate they should be used for topographic and morphological examinations.

Detecting chloroquine retinopathy: electro-oculogram versus colour vision.

AIM: To investigate the relative sensitivity and specificity of two tests of retinal function (the electro-oculogram (EOG) and a computerised colour vision test) in screening for ocular toxicity caused by chloroquine and hydroxychloroquine. METHODS: 93 patients with rheumatic diseases receiving long term chloroquine and hydroxychloroquine therapy were followed for an average of 2.6 years. Clinical examination, an EOG, and a quantitative test of colour vision were carried out every 6 months. RESULTS: Mild fundus changes were observed in 38 patients. Four patients developed typical bull's eye maculopathy, three of whom had received 250, 365, and 550 g total dose of chloroquine, and one 1500 g of hydroxychloroquine. Statistical analysis of all patients showed that for those with no fundus changes or stippled pigmentation a number showed elevation of tritan threshold, so that if macular stippling is a sign of mild retinopathy the test on tritan changes has a 64% sensitivity and 63% specificity for an upper threshold value of 7%. All four patients with bull's eye lesions showed a marked disturbance of tritan colour vision, with a threshold of 14.8%, a sensitivity of 75%, and a specificity of 94%. For protan colour vision a threshold of 10% gives 75% sensitivity and 91% specificity. By contrast, neither an absolute nor a relative EOG reduction was a valid criterion for early or late chloroquine retinopathy. In advanced retinopathy an Arden coefficient (AQ) <180% yields 50% sensitivity and 54% specificity. When AQ <160% is the threshold, sensitivity does not increase but specificity rises to 82%. Occurrence of marked corneal deposits on clinical examination yields 50% sensitivity and 90% specificity in this situation. CONCLUSION: Screening for chloroquine retinopathy can be improved by using a sensitive colour test. Disturbance of the tritan axis appears to occur first. A normal test result on computerised colour testing virtually excludes any retinopathy by antimalarials. The EOG is of little diagnostic value.

Melanoma inhibitory activity: a novel serum marker for uveal melanoma.

The aim of this study was to evaluate the tumour-associated antigen melanoma inhibitory activity (MIA) as a potential novel serological tumour marker in primary and metastatic uveal melanoma in both the laboratory and the clinical setting. In the laboratory setting, immunohistochemical staining with MIA antibody was performed in paraffin-embedded tissues from six amelanotic uveal melanomas and eight metastatic lesions of uveal melanomas. In the clinical setting, serum samples of 139 patients with uveal melanoma were examined; eight of these patients had overt metastatic disease. Sixty-one initially metastatic disease-free patients were followed over time (median follow-up 240 days, 95% confidence interval 60-883 days) and MIA levels were assessed repeatedly. A one-step enzyme-linked immunosorbent assay was used to quantify the MIA serum levels. In the laboratory setting, five of the six primary uveal melanomas and seven of the eight metastatic lesions stained immunohistologically positive for MIA. In the clinical setting, the 131 patients without overt metastatic disease demonstrated a median serum concentration of MIA of 6.6 ng/ml. In the eight patients with overt metastatic disease, the median serum concentration of MIA was 26.28 ng/ml. This difference was highly statistically significant (P < 0.001, analysis of variance). During follow-up, three initially metastatic disease-free patients developed overt metastatic disease, and the MIA level increased from a median of 6.6 ng/ml before to 29.2 ng/ml after clinical detection of metastatic disease. In the 58 other patients, the serum level remained stable during the entire follow-up period. In conclusion, MIA is expressed in primary and metastatic lesions of uveal melanomas, and a statistically significant elevation in MIA serum levels in patients who develop metastatic disease due to uveal melanoma indicates its promising role as a serum marker for monitoring uveal melanoma patients for metastasis.

Central corneal thickness measurement with a retinal optical coherence tomography device versus standard ultrasonic pachymetry.

PURPOSE: To demonstrate the capability of a standard, commercially available optical coherence tomography device (originally designed to measure retinal thickness) to image the human cornea in vivo and to measure central corneal thickness (CCT) in normal and edematous corneas. The intrapatient precision and interpatient variability of this novel application was compared to standard ultrasonic pachymetry. Also, the correlation of both methods was investigated. METHODS: CCT measurements using optical coherence tomography (OCT) and ultrasonic pachymetry (PACH) were obtained in 36 normal eyes and 16 eyes with corneal edema. RESULTS: Direct in vivo imaging of the cornea and measurements of CCT by OCT could be performed in all eyes. In normal subjects, CCT(OCT) was 530+/-32 microm and CCT(PACH) was 581+/-34 microm. The two methods showed a highly significant correlation with a standardized regression coefficient of 0.988. The difference between both methods was constant over the range of CCT (mean difference, 49.4+/-5.9 microm). The mean intrapatient SD of CCT measurements was 4.90 microm and 4.96 microm for OCT and PACH, respectively. In patients with corneal edema, mean CCT(OCT) was 601+/-59 microm, and mean CCT(PACH) was 667+/-68 microm. The difference between the two techniques increased slightly with increasing corneal edema (mean difference, 66.9+/-10.9 microm). CONCLUSION: Imaging of the human cornea can be performed by a standard retinal OCT device, and OCT measurement of CCT shows excellent correlation to values obtained by PACH, giving similar readings separated by a constant difference. In corneal edema, the difference between the two methods is additionally increased, but continues to demonstrate excellent consistency.