Karl Kircher

Local Tumor Control, Visual Acuity, and Survival After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

PURPOSE To evaluate long-term local tumor control, visual acuity, and survival after hypofractionated linear accelerator-based stereotactic photon radiotherapy in patients with choroidal melanoma. METHODS AND MATERIALS Between 1997 and 2007, 212 patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at a linear accelerator with 6-MV photon beams at the Medical University of Vienna in five fractions over 7 days. Twenty-four patients received a total dose of 70 Gy (five fractions of 14 Gy), 158 a total dose of 60 Gy (five fractions of 12 Gy) and 30 patients a total dose of 50 Gy (five fractions of 10 Gy) applied on the 80% isodose. Ophthalmologic examinations were performed at baseline and every 3 months in the first 2 years, every 6 months until 5 years, and once a year thereafter until 10 years after radiotherapy. Assessment of visual acuity, routine ophthalmologic examinations, and measurement of tumor base dimension and height using standardized A-scan and B-scan echography were done at each visit. Funduscopy and fluorescein angiography were done when necessary to document tumor response. RESULTS Median tumor height and volume decreased from 4.8 mm and 270.7 mm3 at baseline to 2.6 mm and 86.6 mm3 at the last individual follow-up, respectively (p<0.001, p<0.001). Median visual acuity decreased from 0.55 at baseline to hand motion at the last individual follow-up (p<0.001). Local tumor control was 95.9% after 5 years and 92.6% after 10 years. Thirty-two patients developed metastatic disease, and 22 of these patients died during the follow-up period. CONCLUSION Hypofractionated stereotactic photon radiotherapy with 70 to 50 Gy delivered in five fractions in 7 days is sufficient to achieve excellent local tumor control in patients with malignant melanoma of the choroid. Disease outcome and vision are comparable to those achieved with proton beam radiotherapy. Decreasing the total dose below 60 Gy seems to be possible.

Reproducibility of high-resolution optical coherence tomography measurements of the nerve fibre layer with the new Heidelberg Spectralis optical coherence tomography

Aim Conventional time-domain OCT technology for detection of retinal nerve fibre layer (RNFL) neurodegeneration suffers from technical inaccuracy owing to a lack of exact scan centring around the optic disc as well as a true follow-up possibility. In this study, the authors evaluated a novel high-resolution spectral-domain OCT device (SD-OCT) with an incorporated eye-tracking feature in its ability to objectively measure the RNFL thickness (RNFLT) by testing intraobserver reproducibility in a series of healthy volunteers. Methods Triplicate circumferential RNFL scans of six peripapillary sectors were obtained from both eyes of all 31 participants. The authors compared the measurements of RNFLT during three separate examination days under miotic (Mi) and mydriatic (My) pupil conditions using a high-speed (HS) and high-resolution (HR) scan-acquisition mode. To examine the intersession reproducibility of the SD-OCT measurements, the mean, SD and coefficient of variation (COV) were calculated. Results No significant differences were found in all groups, independent of the mode of image acquisition and examination day (p always >0,05). Under all conditions, low COVs between 0.545% and 3.97% (intrasession COV on baseline) were found. The intersession COV with activated follow-up mode ranged between 0.29% and 1.07%. In both settings, the temporal sector showed the highest COV values. Conclusions True follow-up measurement of identical peripapillary regions may enable clinicians to detect discrete levels of retinal thickness change over time. This constitutes a crucial prerequisite for a reliable monitoring of subtle RNFL changes in neurodegenerative disorders.

Heterogeneous Pattern of Retinal Nerve Fiber Layer in Multiple Sclerosis. High Resolution Optical Coherence Tomography: Potential and Limitations

Background Recently the reduction of the retinal nerve fibre layer (RNFL) was suggested to be associated with diffuse axonal damage in the whole CNS of multiple sclerosis (MS) patients. However, several points are still under discussion. (1) Is high resolution optical coherence tomography (OCT) required to detect the partly very subtle RNFL changes seen in MS patients? (2) Can a reduction of RNFL be detected in all MS patients, even in early disease courses and in all MS subtypes? (3) Does an optic neuritis (ON) or focal lesions along the visual pathways, which are both very common in MS, limit the predication of diffuse axonal degeneration in the whole CNS? The purpose of our study was to determine the baseline characteristics of clinical definite relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients with high resolution OCT technique. Methodology Forty-two RRMS and 17 SPMS patients with and without history of uni- or bilateral ON, and 59 age- and sex-matched healthy controls were analysed prospectively with the high resolution spectral-domain OCT device (SD-OCT) using the Spectralis 3.5mm circle scan protocol with locked reference images and eye tracking mode. Furthermore we performed tests for visual and contrast acuity and sensitivity (ETDRS, Sloan and Pelli-Robson-charts), for color vision (Lanthony D-15), the Humphrey visual field and visual evoked potential testing (VEP). Principal Findings All 4 groups (RRMS and SPMS with or without ON) showed significantly reduced RNFL globally, or at least in one of the peripapillary sectors compared to age-/sex-matched healthy controls. In patients with previous ON additional RNFL reduction was found. However, in many RRMS patients the RNFL was found within normal range. We found no correlation between RNFL reduction and disease duration (range 9–540 months). Conclusions RNFL baseline characteristics of RRMS and SPMS are heterogeneous (range from normal to markedly reduced levels).

In vivo identification of alteration of inner neurosensory layers in branch retinal artery occlusion

Background/aims To characterise the extension and progression of alteration of neurosensory layers following acute and chronic branch retinal artery occlusion (BRAO) in vivo using spectral-domain optical coherence tomography. Methods In this observational case series, eight eyes with acute BRAO and nine eyes with chronic BRAO were analysed using a Spectralis Heidelberg Retina Angiograph (HRA)+optical coherence tomography system including eye tracking. Patients with acute BRAO were examined within 36±5 h after primary event and at weekly/monthly intervals thereafter. Segmentation measurements of all individual neurosensory layers were performed on single A-scans at six locations in affected and corresponding non-affected areas. The thickness values of the retinal nerve fibre layer together with the ganglion cell layer (NFL/GCL), inner plexiform layer (IPL), inner nuclear layer together with outer plexiform layer (INL/OPL), outer nuclear layer (ONL), and photoreceptor layers together with the retinal pigment epithelium (PR/RPE) were measured and analysed. Results Segmentation evaluation revealed a distinct increase in thickness of inner neurosensory layers including the NFL/GCL (35%), IPL (80%), INL/OPL (48%) and mildly the ONL by 21% in acute ischaemia compared with corresponding layers in non-ischaemic areas. Regression of intraretinal oedema was followed by persistent retinal atrophy with loss of differentiation between IPL and INL/OPL at month 2. In contrast, the ONL and subjacent PR/RPE retained their physiological thickness in patients with chronic BRAO. Conclusion In vivo assessment of retinal layer morphology allows a precise identification of the pathophysiology in retinal ischaemia.

Effect of Age on Antibody Titer to Mycoplasma pneumoniae

Between January 1996 and September 1999, 13,650 serum samples from 12,337 patients were examined for antibodies to Mycoplasma pneumoniae at the Institute of Hygiene, University Hospital Vienna in the course of routine diagnosis. Antibody determination was performed by means of the microparticle agglutination assay Serodia Myco? II. Overall, positive results (antibody titer ≥ 1 : 40) were obtained in 2028 patients (16.4%). Age details were available for analysis in 2016 positive patients. Young children (≤⃒ 9 y) who tested positive showed a geometric mean titer of 1 : 137.9 (95% confidence interval: 117.7-161.4). The geometric mean titers of positive patients decreased significantly with age (Spearmans correlation coefficient - 0.20; p < 0.0001). Only 1/87 patients with serological evidence of M. pneumoniae infection aged ≥ 70 y showed a titer of ≥ 1 : 320. These data highlight the fact that, in the elderly, acute M. pneumoniae infection has to be considered in cases with slightly elevated antibody titers, which are usually referred to as borderline in children and young adults.

Radiogenic Side Effects After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

PURPOSE To evaluate side effects of hypofractionated stereotactic photon radiotherapy for patients with choroidal melanoma. PATIENTS AND METHODS Two hundred and twelve patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at the Medical University of Vienna between 1997 and 2007 with a Linac with 6-MV photon beams in five fractions with 10, 12, or 14 Gy per fraction. Examinations for radiogenic side effects were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and then once a year thereafter until 10 years after radiotherapy. Adverse side effects were assessed using slit-lamp examination, funduscopy, gonioscopy, tonometry, and, if necessary, fundus photography and fluorescein angiography. Evaluations of incidence of side effects are based on an actuarial analysis. RESULTS One hundred and eighty-nine (89.2%) and 168 (79.2%) of the tumors were within 3 mm of the macula and the optic disc, respectively. The five most common radiotherapy side effects were retinopathy and optic neuropathy (114 cases and 107 cases, respectively), cataract development (87 cases), neovascular glaucoma (46 cases), and corneal epithelium defects (41 cases). In total, 33.6%, 38.5%, 51.2%, 75.5%, and 77.6% of the patients were free of any radiation retinopathy, optic neuropathy, cataract, neovascular glaucoma, or corneal epithelium defects 5 years after radiotherapy, respectively. CONCLUSION In centrally located choroidal melanoma hypofractionated stereotactic photon radiotherapy shows a low to moderate rate of adverse long-term side effects comparable with those after proton beam radiotherapy. Future fractionation schemes should seek to further reduce adverse side effects rate while maintaining excellent local tumor control.

Hypofractionated stereotactic photon radiotherapy of posteriorly located choroidal melanoma with five fractions at ten Gy – Clinical results after six years of experience

PURPOSE To evaluate long-term safety and efficacy of hypofractionated stereotactic photon radiotherapy with 5 five fractions at 10 Gy each in patients with centrally located choroidal melanoma. MATERIALS AND METHODS Ninety-one patients with centrally located choroidal melanoma were treated stereotactically at a linear accelerator with 6 MV photon beams with 5 fractions at 10 Gy each. Examinations were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and yearly thereafter. Median follow-up was 37.8 months (IQR 19.2-49.9). They included visual acuity assessment, routine ophthalmological examinations with fundoscopy, echography for measurement of tumor dimensions, medical examinations and, if necessary, fluorescein angiography. RESULTS Initial tumor base diameters, height and volume were 11.20mm (IQR 9.10-13.70), 9.80 mm (IQR 7.80-11.70), 4.53 mm (IQR 3.33-6.43) and 253.8mm(3) (IQR 127.5-477.0). Local tumor control and eye retention rates were 97.7% and 86.4% after 5 years, respectively. Eight patients developed metastatic disease and 3 of them died due to metastatic disease during the follow-up period. Median visual acuity decreased from 0.67 initially to 0.05 at the last individual follow-up (p<0.001). The most common toxicities (any grade) were radiation retinopathy (n=39), optic neuropathy (n=32), radiogenic cataract (n=21), neovascular glaucoma (n=15) and dry eye syndrome (n=10). The 5 year probabilities to remain free of these side effects (any grade) were 26.0%, 45.4%, 55.4%, 72.6% and 80.5%, respectively. The most important prognostic factors for toxicities were the largest tumor base diameter, tumor height and tumor distance to the optic disk. CONCLUSION Hypofractionated stereotactic photon radiotherapy with a total dose of 50 Gy delivered in 5 fractions is a highly effective treatment option in patients with centrally located choroidal melanoma and has a moderate toxicity profile.

RNFL thickness in MS-associated acute optic neuritis using SD-OCT: critical interpretation and limitations.

Purpose:  Axonal loss is considered a key prognostic factor in diagnosing and monitoring the progress of multiple sclerosis (MS). The purpose of our research was to determine whether the measurement of retinal nerve fibre layer thickness (RNFLT) as measured with high‐resolution spectral‐domain optical coherence tomography (SD‐OCT) differs between optic nerve injury following acute optic neuritis (ON) or following unregistered subclinical axonal damage in patients with MS.

Immunohistochemical detection of estrogen and progesterone receptor in human cornea

OBJECTIVE For treatment of postmenopausal keratoconjunctivitis sicca hormone therapy is favored by some clinicians. The likely morphological basis assessing the hormone receptor status in the human cornea has not been performed. Immunohistochemical staining methods provide the opportunity to evaluate the hormone receptor content within the histologic compartments of the cornea. The aim of our study was to assess and localize immunohistochemical hormone receptor staining in the human cornea. METHODS Formalin-fixed and paraffin-embedded specimens of three pre- and three postmenopausal women were assessed for localization of estrogen receptor (ER) and progesterone receptor (PR) expression with established immunohistochemical hormone receptor staining methods. RESULTS No nuclear staining reaction was found in the epi- and endothelial layers of the corneas. The stroma of the corneas showed no immunohistochemical staining reaction in all cases. We found cytoplasmatic PR staining of the endothelial layer in two cases. CONCLUSIONS We found no morphological basis in the human cornea for the use of topical steroid hormone treatment in postmenopausal keratoconjunctivitis sicca. Hormone receptor expression in the conjunctiva or in the lacrimal gland may have an impact in some patients showing relief of symptoms in postmenopausal dry eye syndrome.

Ocular arterial blood flow of choroidal melanoma eyes before and after stereotactic radiotherapy using Leksell gamma knife: 2 year follow up

AIMS To evaluate the effect of high dose stereotactic radiotherapy on the ocular blood flow of patients with uveal melanoma. METHODS Colour Doppler imaging (CDI) was used to measure blood flow velocity and vascular resistance in the ophthalmic, short posterior, and central retinal arteries of nine patients suffering from uveal melanoma. The measurements were taken before, 6 months, 1 year, and 2 years after stereotactic radiotherapy. Irradiation was performed with the Leksell gamma knife with the 59 (41–66.5) Gy total marginal dose divided in two equal fractions. CDI results were compared with age and sex matched healthy control eyes. RESULTS At each time of measurement, blood flow velocity in the central retinal artery of the affected eyes was significantly reduced whereas vascular resistance was only increased at the 2 year follow up. Blood flow velocity and vascular resistance in the short posterior arteries of melanoma eyes were also only significantly altered at the 2 year follow up. Blood flow velocity and vascular resistance in the ophthalmic artery of melanoma eyes were not changed at all follow ups. CONCLUSIONS In the melanoma eyes, blood flow velocity in the central retinal artery is reduced. High dose stereotactic radiotherapy with the Leksell gamma knife and a 59 (41–66.5) Gy total marginal dose in two fractions leads to a significant reduction of blood flow and a significant increase in resistance variables in the small ocular arteries within 2 years.