Evaluation of Choroidal Melanoma Vascularization by Color Doppler Flow Imaging: An Option for Follow-Up Tumor Control Assessment after CyberKnife®?

Background and Objectives: Thus far, tumor control for choroidal melanoma after teletherapeutic radiation is clinically difficult. In contrast to brachytherapy, the tumor height does not necessarily have to shrink as a result of teletherapy. Therefore, the objective of this study was to evaluate tumor vascularization determined by color Doppler flow imaging (CDFI) as a possible approach for monitoring the therapy response after teletherapy of choroidal melanoma. Materials and Methods: A single-center retrospective pilot study of 24 patients was conducted, all of whom had been diagnosed with choroidal neoplasm, treated and followed up. Besides tumor vascularization, the following parameters were collected: age, gender, tumor entity, location, radiation dose, knowledge of relapse, tumor height, radiation-related complications, occurrence of metastases, visual acuity in logMAR. Results: The level of choroidal melanoma vascularization markedly decreased in all included subjects after treatment with the CyberKnife® technology. Initially, the level of vascularization was 2.1 (SD: 0.76 for n = 10); post-therapeutically, it averaged 0.14 (SD: 0.4). Regarding the tumor apex, CDFI sonography also demonstrated a significant tumor regression (mean value pre-therapeutically: 8.35 mm-SD: 3.92 for n = 10; mean value post-therapeutically: 4.86 mm-SD: 3.21). The level of choroidal melanoma vascularization declined in the patient collective treated with ruthenium-106 brachytherapy. The pre-therapeutic level of vascularization of 2 (SD: 0 for n = 2) decreased significantly to a level of 0 (mean: 0-SD: 0). The tumor height determined by CDFI did not allow any valid statement regarding local tumor control. In contrast to these findings, the patient population of the control group without any radiation therapy did not show any alterations in vascularization. Conclusions: Our data suggest that the determination of the tumor vascularization level using CDFI might be a useful and supplementary course parameter in the follow-up care of choroidal melanoma to monitor the success of treatment. This especially applies to robot-assisted radiotherapy using CyberKnife®. Further studies are necessary to validate the first results of this assessment.

Histopathological Features and Ann Arbor Stage in Periocular Lymphoma.

BACKGROUND: To evaluate biodata, symptoms/signs, lymphoma type, localization, stage level, treatment choice and outcome of ocular adnexal lymphoma (OAL). PATIENTS AND METHODS: A single-center retrospective analysis of 56 patients with OAL was performed from 1998 to 2018. RESULTS: OAL involved the orbit in 44.6%, the conjunctiva in 32.1%, the lacrimal apparatus in 14.3% and the eyelid in 8.93%. Extranodal marginal zone B-cell lymphoma (EMZL) was found in 60.7%, follicular lymphoma (FL) in 21.4%, diffuse large B-cell lymphoma in 7.14%, mantle cell lymphoma in 5.36% and chronic lymphatic leukaemia in 5.36% patients. No relapse was seen in 76%. EMZL and FL had a significantly better overall survival compared to other lymphoma types (p=0.002). Patients with Ann Arbor stage IE had a significantly better prognosis than those with stages higher than IE (p=0.048). CONCLUSION: Our data suggest that clinicopathological features such as Ann Arbor stage influence survival.

[Ocular lymphoma : Precise diagnostics and classification as key for successful personalized treatment]. / Lymphom am Auge : Präzise Diagnostik und Klassifikation als Schlüssel einer erfolgreichen personalisierten Therapie.

BACKGROUND: Personalized medicine is nowadays the standard of care for patients with oncological diseases. A prime example is the lymphoma, which has substantial points of contact with ophthalmological care due to the intraocular and periocular involvement. OBJECTIVE: This article provides a description of the current personalized diagnostics and treatment of ocular lymphomas. METHODS: This article constructs a relationship between the current knowledge in the literature, guidelines and recommendations and the clinical experience with ocular lymphomas. It explains in particular the molecular and also individual personalized treatment concepts. RESULTS: The primary suspicion of lymphatic or other ocular oncological diseases is raised by an ophthalmologist based on clinical symptoms. The exact diagnostic procedure is carried out with molecular biological techniques, such as immunohistology and polymerase chain reaction analyses. A staging of the mass is indispensable and the stage classification according to the Ann Arbor criteria for a correct assignment of the lymphoma is of clinical importance. Based on these precise diagnostics an individualized choice of treatment and subsequent personalized follow-up care are carried out. During the complete process from the diagnostic procedure to treatment and aftercare, psycho-oncological support should be offered to the patient. CONCLUSION: Personalized medicine is already actively performed in the care of ocular lymphomas. The patient is in the forefront and plays a decisive role. By considering the special features of the tumor and patient parameters, the life expectation and relapse-free interval as well as quality of life have been improved for many types of lymphoma. It must be assumed that these advantages also apply to ophthalmology.

[Alternative treatment options for periorbital basal cell carcinoma]. / Alternative Behandlungsoptionen beim Basalzellkarzinom am Auge.

BACKGROUND: Latest developments as well as established procedures offer alternative treatment approaches to basal cell carcinoma (BCC) when micrographically controlled surgical removal is not a valid option. OBJECTIVE: Alternative treatment options for periorbital BCC are presented. METHODS: A literature search was carried out and a structured display and analysis of the results are given. RESULTS: Micrographically controlled surgical removal represents the gold standard in treatment of BCC. When for various reasons surgical removal is not a valid option, other procedures are required. The alternative treatment options can be divided into three main groups: treatment options for locally advanced or metastasized BCC, topical approaches for small and superficial BCC and prophylactic measures. While radiotherapy and systemic therapy are suitable for locally advanced BCC and are discussed in a tumor board, small and superficial BCC can be treated by topical medication. In cases of a previous BCC history, a prophylactic treatment can be considered. Combinations of systemic treatment and also neoadjuvant or adjuvant approaches before and after surgery are promising options for a successful outcome, which can further improve the standard treatment for locally advanced BCC. CONCLUSION: Alternative treatment options for periocular BCC are available; however, the use is only indicated when microscopically controlled excision with subsequent oculoplastic reconstruction is not possible. According to the national guidelines a prior presentation to a suitable tumor board is practically compulsory.

GEE approaches to marginal regression models for medical diagnostic tests.

The evaluation of a new medical diagnostic test may focus on two different scientific questions: (1). The new test may replace an existing one because of lower cost or higher validity. A related question would be the selection of the 'best' test(s) from a bundle of new or established measurements. (2). The new test may be used supplementary to other new or established procedures. In a recent publication, Leisenring and co-workers (Stat Med 1997; 16:1263-1281) developed a general marginal regression model for comparisons of diagnostic tests focussing on question (1). i.e. on the selection of the 'best' procedure. They applied the GEE approach of Liang and Zeger (Biometrika 1987; 73:13-22) to adjust for the correlation of data as a nuisance parameter. Using the general framework provided by Leisenring et al., we extend their approach and apply the GEE methodology to question (2). i.e. to the investigation of which of several diagnostic tests should be used supplementary to each other. We analyse data from a longitudinal study concerning pathogenesis, diagnosis and long-term course of the eye disease glaucoma. We find a dependence of the correlation structure of several diagnostic measurements on the severity of the disease. This result may be useful in clinical applications as regards the selection of subsets of diagnostic measurements in individual diagnostic processes but also in investigations concerning the relationship of the pathogenic process and the rationales of the different diagnostic procedures.

Stereoscopic visual evoked potentials in normal subjects and patients with open-angle glaucomas.

PURPOSE: To evaluate stereoscopic visual evoked potentials (S-VEP) in normal controls and in patients with glaucomatous optic nerve damage. METHODS: Computer-generated dynamic random-dot stereograms were used to elicit cortical visual evoked potentials using wireless electric liquid crystal shutter glasses. Normal subjects (n=22) and patients with glaucoma (n=22) were investigated using five different disparities from 9 to 40 arc min. Statistical dependency of measurements with different stimulus at identical patients was adjusted for. RESULTS: Peak times of onset and offset response of S-VEP can be significantly delayed in glaucomas. A general linear regression model confirmed that differences between patients and normals depend on disparity. S-VEP onset shows no significant difference between controls and glaucomas at 9 arc min disparity. At high disparities, however, peak time of the onset response was significantly (p<0.01) delayed in glaucomas when compared with normals (normals: 125.8+/-13 ms, glaucomas: 148.2+/-25.6 ms at 40 arc min). CONCLUSIONS: Visual evoked potential elicited by the onset of a random-dot stereogram can be used for objective measurement of stereoacuity in a clinical setting. Differences between controls and glaucomas in high and low disparities could indicate a stereo-specific deficit in glaucoma.

[Comparison of precision of the TonoPenXL with the Goldmann and Draeger applanation tonometer in a sitting and recumbent position of the patients -- a clinical study on 251 eyes]. / Vergleich der Präzision des TonoPenXL bei Liegend- und Sitzendmessung mit den Applanationstonometern nach Goldmann und Draeger -- eine klinische Studie an 251 Augen.

PURPOSE: Comparison of precise intraocular pressure (IOP) measurement with TonoPenXL, Goldmann and Draeger applanation tonometer in a sitting and recumbent position. MATERIAL AND METHODS: The IOP of 251 eyes of 127 consecutive patients (SFB 539) was measured prospectively in a sitting position (1 x Goldmann, 3 x TonoPenXL) and in recumbent position (1 x Draeger, 3 x TonoPen). The mean of three TonoPenXL measurements was only accepted in a 5 % interval. Additionally, corneal ultrasonic pachymetry (Tomey, AL-2000), central corneal power, refractive error, gender and age were registered. RESULTS: The IOP measured with the TonoPenXL was in 92 % in a range of 2 mm Hg from the Goldmann standard. In a vertical position, the IOP TonoPenXL (16.7 +/- 4.5 mm Hg) was 0.2 mm Hg lower than the IOP Goldmann (16.9 +/- 5.1 mm Hg; regression analysis: IOP TonoPenXL = 1.78 + 0.88 IOP Goldmann). In a horizontal position, the IOP TonoPenXL (17.5 +/- 5.0 mm Hg) was 0.5 mm Hg higher as the IOP Draeger (17.0 +/- 5.3 mm Hg; regression analysis: IOP TonoPen = 0.34 + 1.016 IOP Draeger). Using the TonoPenXL, the IOP was 0.8 mm Hg higher in recumbent position than in a sitting position (regression analysis: IOP TonoPen recumbent position = - 2.27 + 1.19 IOP TonoPen sitting position). We found no relationship found between central corneal power, central corneal thickness and IOD measured with the TonoPenXL. CONCLUSIONS: The TonoPenXL is useful for IOP measurement in a sitting and recumbent position. The results are reproducible in 92% with the Goldmann-applanation tonometer. The ophthalmologist has a comfortable measurement and screening tool for consultations or IOP investigation under general anaesthesia.

Novel mutations in the MYOC/GLC1A gene in a large group of glaucoma patients.

Mutations at the myocilin (MYOC) gene within the GLC1A locus have been revealed in 2-4% of patients suffering primary open angle glaucoma (POAG) worldwide. In our ongoing glaucoma study six hundred eighty two persons have been screened for MYOC mutations. The first group consisted of 453 patients from a long-term clinical study diagnosed either with juvenile OAG (JOAG), POAG, ocular hypertension (OHT) or normal tension glaucoma (NTG) plus 22 cases of secondary glaucoma. This group, and additional 83 healthy controls, is part of a long term study with repeated clinical examinations at the University of Erlangen-Nurnberg. An additional sample of 124 glaucoma patients or at risk persons referred from other sources were included in the mutation screening. Five novel mutations, namely Gly434Ser, Asn450Asp, Val251Ala, Ile345Met and Ser393Asn, could be identified as cause of preperimetric POAG, JOAG, normal tension POAG and POAG. Myocilin mutations were identified similar with previous reports with other ethnic populations at the rate of 11/341 (3.2%) probands.

Testing for glaucoma with frequency-doubling perimetry in normals, ocular hypertensives, and glaucoma patients.

BACKGROUND: The aim of this study was to evaluate the diagnostic usefulness of the FDT perimeter protocol (C-20-5) in combination with a database system for analysis of single test locations. METHODS: One hundred seventy-three ocular hypertensive eyes, 116 "preperimetric" open-angle glaucoma eyes (glaucomatous optic disc atrophy, elevated intraocular pressure, no visual field defects in standard white-on-white perimetry), 199 "perimetric" open-angle glaucoma eyes (glaucomatous optic disc atrophy and visual field defects), and 151 control eyes underwent FDT screening and conventional white-on-white perimetry. Four repeated measurements were carried out in 15 glaucoma patients at 2-h intervals to judge reproducibility of all test locations. The present screening strategy begins testing at the normal 5% probability level. If a stimulus is not detected, further targets are presented. FDT-Viewfinder and statistics software were used for case-wise recalculation of all missed localized probability levels and correlation with corresponding test locations using conventional perimetry. RESULTS: Analysis of repeated measurements in patients reveals that variation of single test points can be considerable. However, the numbers of missed test-stimuli calculated globally or in quadrants are significantly correlated with corresponding Octopus visual field defects (Spearman rank correlation P<0.001). Using a predefined specificity of 96% in control eyes, 11% of ocular hypertensive eyes, 28.5% of "preperimetric" glaucoma eyes and 86.9% of "perimetric" glaucoma eyes have been classified glaucomatous using an overall score and with consideration of different cut-off points in right and left eyes. CONCLUSION: Point-wise analysis of FDT screening results can be helpful for classification of patient groups and consideration of the individual learning curve in repeated measurements. The C-20-5 protocol of the FDT perimeter is able to detect a considerable proportion of glaucomatous patients.

Monitoring glaucoma progression with visual evoked potentials of the blue-sensitive pathway.

PURPOSE: To determine the value of visual evoked potentials with blue-on-yellow pattern stimulation in follow-up of glaucoma. METHODS: This prospective longitudinal concurrent study included a heterogeneous cohort of two groups, perimetric (n = 161) and preperimetric (n = 118), of patients with chronic open-angle glaucoma and 113 healthy control subjects. In the preperimetric glaucoma group, patients showed glaucomatous abnormalities of the optic disc, maximum intraocular pressure higher than 21 mm Hg, and unremarkable computerized visual field examination results. Patients underwent up to three VEP measurements with blue-on-yellow pattern stimulation, as well as qualitative and morphometric evaluation of color stereo optic disc photographs. Mean follow-up time between measurements was 24 months. VEP measurements were separately analyzed in preperimetric subjects, with and without progression of optic nerve damage. Progression of glaucoma was defined as increasing loss of neuroretinal rim. RESULTS: A separate analysis of VEP peak times in patients in the preperimetric group, with and without progression of glaucomatous optic nerve damage, showed no significant difference at baseline but a significant prolongation (P = 0.01) in patients with progressive disease, 2 years before morphologic changes were evident. VEPs in patients with nonprogressive disease were statistically unchanged during the observation period. The perimetric group and both preperimetric groups showed significantly prolonged VEP peak times in comparison with the control group (P < 0.001). CONCLUSIONS: In addition to photographic evaluation to detect glaucomatous disc atrophy, the blue-on-yellow VEP may be an objective electrophysiological tool for monitoring patients with glaucoma, because peak times are significantly associated with progression of optic nerve damage.