Uveal melanoma survival rates after single dose stereotactic radiosurgery.

This paper presents the long-term results of single dose stereotactic radiosurgery for intraocular uveal malignant melanoma, and summarizes the results of the retrospective study in 170 Slovak patients. A group of uveal melanoma patients (149 choroidal melanoma, 21 ciliary body melanoma) from 20 to 92 years of age with 59 year median were treated in 2001-2016. There were 81males (47.7%) and 89 females 89 (52.3%). The median overall follow-up time was three years. The median tumor volume at baseline was 0.5 cm³ (ranging from 0.2 to 1.6 cm³). The therapeutic dose was 35.0 Gy by 99% of dose volume histogram. The survival after single dose stereotactic radiosurgery was 96% in one year, 93% in two years, 84% in five years, 80% in seven years and 52% in eleven years. Secondary enucleation was necessary for 22 patients because of secondary glaucoma complication. The enucleation free interval ranged from one to six years. The survival rates in five year intervals and necessity of secondary enucleation due to complications after single dose stereotactic radiosurgery is comparable to other techniques.

Is it sufficient to repeat LINEAR accelerator stereotactic radiosurgery in choroidal melanoma?

OBJECTIVES: One day session LINAC based stereotactic radiosurgery (SRS) at LINAC accelerator is a method of "conservative" attitude to treat the intraocular malignant uveal melanoma. METHODS: We used model Clinac 600 C/D Varian (system Aria, planning system Corvus version 6.2 verification IMRT OmniPro) with 6 MeV X by rigid immobilization of the eye to the Leibinger frame. The stereotactic treatment planning after fusion of CT and MRI was optimized according to the critical structures (lens, optic nerve, also lens and optic nerve at the contralateral side, chiasm). The first plan was compared and the best plan was applied for therapy at C LINAC accelerator. The planned therapeutic dose was 35.0 Gy by 99 % of DVH (dose volume histogram). RESULTS: In our clinical study in the group of 125 patients with posterior uveal melanoma treated with SRS, in 2 patients (1.6 %) was repeated SRS indicated. Patient age of the whole group ranged from 25 to 81 years with a median of 54 TD was 35.0 Gy. In 2 patients after 5 year interval after stereotactic radiosurgery for uveal melanoma stage T1, the tumor volume increased to 50 % of the primary tumor volume and repeated SRS was necessary. CONCLUSION: To find out the changes in melanoma characteristics after SRS in long term interval after irradiation is necessary to follow up the patient by an ophthalmologist regularly. One step LINAC based stereotactic radiosurgery with a single dose 35.0 Gy is one of treatment options to treat T1 to T3 stage posterior uveal melanoma and to preserve the eye globe. In some cases it is possible to repeat the SRS after more than 5 year interval (Fig. 8, Ref. 23).

No differences in outcome between radical surgical treatment (enucleation) and stereotactic radiosurgery in patients with posterior uveal melanoma.

To report the treatment outcome and possible survival difference between radical surgical treatment (enucleation) or stereotactic radiosurgery (SRS). LINAC stereotactic radiosurgery is an alternative treatment for posterior uveal melanoma used in Slovakia since 1999. The study analyzed patients treated for posterior uveal melanoma in the period 2001-2008. The aim of the study was to compare the relapse-free survival in the cohort of patients primarily treated with surgery (enucleation) or SRS. A total number of 84 patients were included, treatment was determined on a case-by-case basis. We reviewed the records of patients with ciliary body or choroidal melanoma treated by enucleation - 44 patients (52%) and SRS - 40 patients (48%). The therapeutic attitude was established on the basis of ophthalmoscopy, ultrasound (A, B mode), other ophthalmological findings, visual acuity, and general status of each patient. Volume of the tumor was calculated using the formula: "pi/6 x length x width x height" for each patient. All of the patients before decision to "conservative" attitude therapy underwent MRI examination. The therapeutic dose in SRS patients group was 35.0-38.0 Gy. The data were analyzed using Kaplan - Meier survival method for the differences in survival rates between the treatment groups, and afterwards by Cox s proportional hazard method with predictors involved. Among the baseline covariates evaluated, only age affected the prognosis for survival to a statistically important, however not significant degree. The risk of death among patients treated with enucleation relative to those treated with stereotaxy after adjustment for baseline characteristics of patients, age, and tumor volumes was not significant [1.82] (95% CI, 0.46 to 7.30; P = 0.396). The overall five-year survival rate for patients with posterior uveal melanoma was 72%. Treatment by either primary enucleation or SRS according to our results does not appear to influence the development of metastases in patients with uveal melanoma; the survival prognosis is essentially determined by the stage and character of the tumor. No survival difference attributable to stereotactic irradiation of uveal melanoma has been demonstrated in this retrospective study. A small difference is possible, but a clinically meaningful difference in mortality rates, whether from all causes or from metastatic melanoma, is unlikely. Treatment by either radical surgical attitude (enucleation) or "conservative" LINAC- SRS does not appear to influence the survival rate in patients with uveal melanoma.

Effective Tissue Layer Separation of Donor Cornea for DMEK by Fluid Injection Between Descemet Membrane and Corneal Stroma: Results of First Series of Operations

AIM: To evaluate clinical outcomes of Descemet Membrane Endothelial Keratoplasty (DMEK) using a novel hydro-separation of donor Descemet membrane (DM) endothelial graft with 6 months follow up. MATERIAL AND METHODS: In this retrospective single-center; single surgeon cohort study, 16 consecutive eyes underwent DMEK or combined DMEK and cataract surgery with DMEK donor graft hydro-separation. The hydroseparation method used Ringer's solution injected by a syringe with a flat end cannula between DM and corneal stroma to separate DMEK graft from donors' cornea. Endothelial cell count, corrected and uncorrected distance visual acuities (CDVA, UDVA), corneal astigmatism and keratometric values were evaluated before and 6 months after the surgery. RESULTS: DMEK grafts were successfully hydro separated, without a membrane tear in all cases and successful adhesion to recipient corneas was achieved in all cases. Overall CDVA improved significantly (p < 0.0001) from preop.0.69 logMAR (0.45­0.92, 95%CI) to 0.1 logMAR (0.04­0.15) 6 months postop. However UDVA was slightly worse in cataract combined cases 0.38 logMAR (0.18­0.43) vs 0.3 logMAR (0.14­0.61) in DMEK cases at 6 months. Corneal astigmatism K2-K1 improved significantly (p=0.0137) from preop. mean 2.89 D (0.19­0.43) to 0.98 D (0.48­1.48) 6 months postop. CONCLUSION: Hydro-separation is fast and effective donor graft preparation method for DMEK. The DMEK using donor graft hydro-separation results in improved vision and induces a low amount of astigmatism at 6 months follow up. Further clinical data are needed to confirm the success rate and to explore optimization of the selection of IOLs in combined cataract cases

RADIATION MACULOPATHY AFTER ONE-DAY SESSION STEREOTACTIC RADIOSURGERY IN PATIENTS WITH CILIARY BODY AND CHOROIDAL MELANOMA.

INTRODUCTION: Nowadays radiotherapy is the standard treatment care for patients with uveal melanoma. In Slovakia the only one option is a one-day session stereotactic radiosurgery at linear accelerator LINAC. Irradiation of surrounding tissues of the eye and orbit causes radiation complications. One of the most serious and vision-threatening is the radiation retinopathy, which divides into maculopathy and peripheric retinopathy. The clinical signs include microanerysms, teleangiectases, hard exsudates, cotton wool spots and macular edema, neovascularisation, and vitreous hemorrhage. Radiation macular edema can be classified by optical coherence tomography into cystoid or noncystoid edema. On fluorescein angiography macular edema is divided into non-ischemic and ischemic, while the latter means usually irreversible loss of the visual acuity. This paper is focused on risk factors of radiation retinopathy although it strongly influences functional result of radiotherapy and preservation of the visual acuity. PURPOSE: By means of bivariate and multivariate analysis to determine the association of radiation dose and other variables with the development of radiation maculopathy. MATERIAL AND METHODS: The retrospective analysis of 168 patients with ciliary body or choroidal melanoma who performed one-day session stereotactic radiosurgery on a linear accelerator LINAC in a period 2007-2016. RESULTS: The prevalence of the radiation maculopathy was 29% with the median time from the irradiation to maculopathy 16 months. Median radiation dose on the macula was 37 Gy. Variables statistically significantly associated with the maculopathy were: radiation dose (p = 0.0016), postequatorial location of the tumor (p = 0.0271) and better visual acuity before treatment (p = 0.0007). The tumor touch of the macula was strongly associated with the visual acuity in the bivariate analysis (p = 0.0006), thus it could be omitted from the final model. DISCUSSION: The radiation dose on a macula is the key determinant for radiation-induced maculopathy, according to other authors and our study approvingly. Other variables were related to proximity of the tumor to the macula, so the radiation dose on the macula was higher indirectly. Better visual acuity before treatment as a risk factor for maculopathy can be a consequence of: a) earlier diagnostics of tumor with proximity to the posterior pole, b) lower enucleation rate; frequency of the enucleation was 1.6 higher in patients without maculopathy. Naturally, on enucleated eyes maculopathy was not diagnosed. Five patients underwent intravitreal application of the bevacizumab as a treatment of the radiation maculopathy, without improvement of the visual acuity. CONCLUSION: Radiation complications can be vision and eye threatening. Radiation maculopathy is a consequence of higher radiation dose on the macula. The treatment modalities of radiation maculopathy are rather ineffective.

Ciliary body melanoma treatment by stereotactic radiosurgery.

INTRODUCTION: Malignant melanoma of the ciliary body (corpus ciliare) represents 10 to 15 percent of tumors of the uveal tract. The aim of the work is to evaluate the effectiveness of stereotactic radiosurgery performed on LINAC linear accelerator and the occurrence of postoperative complications. MATERIAL AND METHODS: Retrospective analysis of patients with ciliary body melanoma treated with stereotactic radiosurgery on linear accelerator in the period 1/2011 to 12/2016 in Slovakia. RESULTS: From 1/2011 to 12/2016 a group of 27 patients with melanoma of the ciliary body underwent one day session stereotactic radiosurgery irradiation on linear accelerator (SRCH). Primary enucleation was indicated in 10 (37 %) patients. A group of 17 (63 %) patients were treated with stereotactic radiosurgery. In a group of 17 patients indicated for SRCH, 7 (41 %) were diagnosed in T1 stage, 8 (47 %) in T2 stage. In 2 (12 %) patients who refused primary enucleation, palliative irradiation was indicated in T3 stage, and later metastases appeared in liver and systemic chemotherapy was indicated. The therapeutic dose in all patients was TD 35 Gy, TD max 42 Gy. The mean age of patients at the time of irradiation was 60.8, the youngest patient was 40 and the oldest was 80 years old. The follow-up period was 12 months to 5 years. CONCLUSION: Currently, in Slovakia, the only irradiation possibility to treat ciliary body melanoma is stereotactic radiosurgery. In our group of 17 patients, this method appears to be effective in the treatment of T1 to T2 stage. The results are comparable to brachytherapy and proton beam irradiation therapy. Key words: corpus ciliare, uveal melanoma, linear accelerator, stereotactic radiosurgery.

Is combination therapy with betalactam plus aminoglycoside (AGL) improving the outcome of nosocomial meningitis in children?

We have been unable to document a benefit of a combination of aminoglycosides with betalactam or carbapenem antibiotics in nosocomial meningitis. This was similar to the cases of sepsis, where survival of patients did not improve with combination therapy. Combination therapy did not increase the chance of appropriateness of the therapy. 30% of those on combination therapy were considered as inappropriately treated in comparison to 2.8% of those on monotherapy (p<0.01).

Postsurgical meningitis caused by Acinetobacter baumannii associated with high mortality.

Twenty five (25) cases of nosocomial postsurgical meningitis due to Acinetobacter baumannii meningitis were compared to other 146 cases of meningitis after surgery caused by other pathogens. Prior neurosurgical ventriculo-peritoneal shunt insertion and CNS abnormality as well as very low birth weight were significant risk factors for acquisition of Acinetobacter baumannii meningitis. Mortality - 40% among children with nosocomial meningitis was unacceptably high and significantly higher than among meningitis caused by microorganisms other than Acinetobacter baumannii.

National 14 years survey of 171 cases nosocomial meningitis in children and comparison of two periods 1993-1998 to 1999-2006.

In 1993-1998 and in 1999-2004 we have performed two surveys of pediatric bacterial meningitis in all 8 neurosurgery/pediatrics and infectious diseases departments in Slovakia. We have detected 101 and another 54 cases with attributable mortality of 15% and sequellae in 18%.

Infectious embolisation to the central nervous system from endocarditis: analyses of 99 cases.

Within a cohort of 606 cases of infective endocarditis, 263 were complicated and 99 embolizing, of them 32 to the central nervous system (CNS). Significant predictors of CNS embolisation were inappropriate therapy (p<0.01) and enterococcal etiology (p<0.01). Mortality in patients with CNS emboli was 65% what was significantly higher than in cases without embolisation - 15% (p<0.01).

Neuroinfections complicating foreign body implants after perinatal trauma or meningitis in 60 children.

Meningitis after artificial implants in 60 children, mainly after foreign body infections (FBI) was caused more frequently by coagulase negative staphylococci and Ps. aeruginosa than other organisms and was significantly associated with perinatal trauma, hydrocephalus, haemorrhage or VLBW and had more neurologic sequels despite mortality was similar to other nosocomial meningitis.

Bacterial meningitis after sinusitis and otitis media: ear, nose, throat infections are still the commonest risk factors for the community acquired meningitis.

We investigated how many cases of bacterial meningitis in our national survey were associated with sinusitis or otitis media. Among 372 cases of bacterial meningitis within our nationwide 17 years survey, 201 cases were community acquired (CBM) and in 40 (20%) otitis media or sinusitis acuta/chronica were reported 1-5 weeks before onset of CBM. Diabetes mellitus (20% vs. 7.5%, p=0.01), alcohol abuse (35% vs. 15.4%, p=0.003) and trauma (30% vs. 14.9%, p=0.02) were significantly associated with CBM after ENT infections. Concerning etiology, CBM after sinusitis/otitis was insignificantly associated with pneumococcal etiology (50% vs. 33.8 %, NS) and significantly associated with other (L. monocytogenes, Str. agalactiae) bacterial agents (9.9 % vs. 25 %, p=0.008) . However those significant differences for new ENT related CBM had no impact on mortality (12.4 % vs. 5%, NS), failure after initial antibiotics (10 % vs. 9.5%, NS) and neurologic sequellae (12.5 % vs. 15.4 %, NS).

Predictors of inferior outcome in community acquired bacterial meningitis.

The aim of this study was to assess mortality and sequellae within cases from Nationwide survey of community acquired meningitis and identify risk factors for inferior outcome. Risk factors such as underlying disease (diabetes mellitus, cancer, trauma, neonatal age, splenectomy, alcoholism, sepsis, other infections), etiology, clinical symptoms and outcome (death, improvement and cured after modifications of ATB therapy, cured without change of therapy, cured with neurologic sequellae) were recorded and analysed with univariate analysis (chi2 or t test for trends, CDC Atlanta 2004). Analysing risk factors for inferior outcome (death or cured with neurologic sequellae), we compared patients who died or survived with neurologic sequellae to all patients with community acquired bacterial meningitis. Univariate analysis showed that trauma (p<0.05), alcohol abuse (p<0.05), diabetes, S. aureus (p<0.05) and gram-negative etiology (A. baumannii, Ps. aeruginosa or Enterobacteriaceae) (36% vs. 11,9%, p<0.05) were predicting inferior outcome. Analysing risk factors for treatment failure (death or failed but cured after change of antibiotic treatment) prior sepsis (34.1% vs. 13.9%, p<0.01) and gram-negative etiology (25% vs. 11.9%, p<0.02) were statistically significant predictors of treatment failure. Neisseria meningitis had less failures (p<0.05). Concerning infection associated mortality again diabetes mellitus (p<0.05), alcoholism (p<0.05) staphylococcal and gram-negative etiology (p<0.05) were significant predictors of death. N. meningitis had surprisingly less treatment failures (appropriate and rapid initial therapy). Neurologic sequellae were more common in patients with alcohol abuse (p<0.05), craniocerbral trauma (p<0.05) and less common in meningitis with pneumococcal etiology (p<0.05).

Comparison of postsurgical and community acquired bacterial meningitis--analysis of 372 cases within a nationwide survey.

The aim of this study was to assess if differences in etiology and risk factors among 372 cases of bacterial meningitis acquired after surgery (PM) or in community (CBM) have impact on outcome of infected patients. Among 372 cases of bacterial meningitis within last 17 years from 10 major Slovak hospitals, 171 were PM and 201 CBM. Etiology, risk factors such as underlying disease, cancer, diabetes alcoholism, surgery, VLBW, ENT infections, trauma, sepsis were recorded and mortality, survival with sequellae, therapy failure were compared in both groups. Significant differences in etiology and risk factors between both groups were reported. Those after neurosurgery had more frequently Coagulase negative staphylococci (p<0.001), Enterobacteriaceae (p=0.01) and Acinetobacter baumannii (p=0.0008) isolated from CSF and vice versa Streptococcus pneumoniae (p<0.001), Neisseria meningitis (p<0.001) and Haemophillus influenza (p=0.0009) were more commonly isolated from CSF in CBM. Neurosurgery (p<0.001), sepsis (p=0.006), VLBW neonates (p=0.00002) and cancer (p=0.0007) were more common in PM and alcohol abuse (p<0.001) as well as otitis/sinusitis (p<0.001) and Roma ethnic group (p=0.001) in CAM. Initial treatment success was significantly more frequently observed among CAM (p<0.001) but cure after modification was more common in PM (p=0.002). Therefore outcome in both groups was similar (14.6% vs. 12.4%, p=NS).

Bacterial meningitis after craniocerebral trauma in the community.

Craniocerebral trauma is one of major risk factors for development of meningitis. We reviewed 30 cases of bacterial meningitis occurring in community after craniocerebral trauma. Alcohol abuse was significant risk factor occurring in trauma patients with meningitis present in 50% in our cohort (p=0.0001). The most common pathogen in posttraumatic meningitis was Str. pneumoniae (90% vs. 33.8%, p=0.0001). However mortality was very low, only 5% probably because of early diagnosis and treatment of patients at risk for bacterial meningitis but neurologic sequellea were significantly more common (p=0.00001) in patients after craniocerebral trauma.

[Possibility of 3D Printing in Ophthalmology - First Experiences by Stereotactic Radiosurgery Planning Scheme of Intraocular Tumor]. / Moznosti 3D tlace v oftalmológii - prvé skúsenosti pri plánovaní stereotaktického rádiochirurgického zákroku u vnútroocného nádoru.

Nowadays 3D printing allows us to create physical objects on the basis of digital data. Thanks to its rapid development the use enormously increased in medicine too. Its creations facilitate surgical planning processes, education and research in context of organ transplantation, individualization prostheses, breast forms, and others.Our article describes the wide range of applied 3D printing technology possibilities in ophthalmology. It is focusing on innovative implementation of eye tumors treatment planning in stereotactic radiosurgery irradiation.We analyze our first experience with 3D printing model of the eye in intraocular tumor planning stereotactic radiosurgery. KEY WORDS: 3D printing, model, Fused Deposition Modelling, stereotactic radiosurgery, prostheses, intraocular tumor.

Complications in patients with uveal melanoma after stereotactic radiosurgery and brachytherapy.

Malignant uveal melanoma is the most common intraocular tumour with the incidence about 0.7-1.0 in 100.000 inhabitants. Enucleation is still a standard treatment method for posterior uveal melanoma, but conservative methods are an adequate alternative. Brachytherapy has been used more than 20 years in our Department, stereotactic radiosurgery was introduced in 1999. In years 1991-2004, 145 patients with uveal melanoma were treated at the Department of Ophthalmology, Comenius University, Bratislava. Conservative treatment/brachytherapy is indicated in tumours staged T1-T3. Survival is comparable for all conservative methods. After stereotactic radiosurgery (Linac), the necessity of enucleation because of complications (e.g. secondary glaucoma), after brachytherapy (Ru106 plaques), it was 5%. Conservative methods and combined techniques are effective methods for the therapy of uveal melanomas (Fig. 5, Tab. 1, Ref. 6).

[Stereotactic Rediosurgery for Uveal Melanoma; Postradiation Complications]. / Stereotaktická rádiochirurgia (LINAC) uveálnych melanómov; postradiacné komplikácie.

OBJECTIVE: The authors evaluate a group of patients with malignant uveal melanoma treated with stereotactic radiosurgery in the year. 2009-2011 on a linear accelerator LINAC. MATERIAL AND METHODS: In 2009-2011 were followed 40 patients with malignant melanoma of the uvea in stage T2 and T3 treated with stereotactic radiosurgery (LINAC), the therapeutic dose of 35,0 Gy TD, TD max 42,0 Gy. We evaluated the influence of factors (age, exposure risk structures, time) to intraocular pressure (IOP) and temporal changes in intraocular pressure after surgery between the control group and the group of patients who underwent enucleation. The normality of data distribution was tested Shapiro-Wilk W test and graphically. The relations between the parameters were tested using simple and multiple linear regression (correlation coefficient r, the significance level p). RESULTS: The mean age of the group of 40 patients with malignant melanoma of the uvea treated by one day session stereotactic radiosurgery on a linear accelerator in the year. 2009-2011 was 55.13±11.11 years. Average maximum radiation dose to sensitive structures has been the target of 12,0 Gy to the optic nerve and the ciliary 10,0 Gy. The analysis in our group confirmed that the prevalence of the tumor independent of sex, increasing with age, with most patients are diagnosed between 60 and 70 years of age. Analysis of the difference in intraocular pressure (IOP) before surgery showed no significant difference between the group of men and women (p=0.54). Using simple linear regression, we confirmed assumptions, related to IOP before stereotactic radiosurgery with age (r=-0.09, p=0.65). Multiple linear regression, we evaluated the relationship between predictors (dose at-risk structures--lens and optic nerve) and the change in IOP from the value before stereotactic radiosurgery at each time interval. Relations between predictors (Dose aperture--L, the dose of the optic nerve--O) and IOP of the file being described partial correlation coefficients after 2 weeks. For the relationship is significant correlation between the dose and the IOP in the lens at the time of 1 year, 1.5 years, and 2 years after the stereotactic radiosurgery. CONCLUSION: A single stereotactic radiosurgery on a linear accelerator LINAC is possible at a dose of 35,0 to 38,0 Gy in intraocular melanomas in stage T1 to T3. According to our results, this is a highly effective method of treatment of uveal melanomas elevation to 6 mm and a capacity of up to 0,4 cm3. Secondary glaucoma is one of the most serious causes of enucleation after one day session stereotactic radiosurgery at linear accelerator (LINAC) for uveal melanoma. The percentage of enucleation in our investigated group (17.5%) for secondary glaucoma is about the same as in other studies.

Critical remarks on the stereotaxic treatment of epilepsy.

The analysis of experiences with 43 patients treated stereotaxically for epilepsy, shows that the stereotaxic method can play an important role 1) in the investigation of the structures in epileptic activity; 2) in proper management of these cases. According to deep electrode records, the epileptic focus seems to be like a system of anatomical structures, which are functionally interdependent, and its relationship can be plotted on a schematic graph, which must be calculated in the strategy of treatment with the combined performances. In spite of this results are not satisfactory. New methodological approaches should be devised, such as longitudinal stereotaxic hippocampectomia, which is suggested as promising.

Herpes simplex virus DNA in the brain of psychotic patients.

Herpes simplex virus (HSV) DNA was found by spot blot hybridization in the right nc. amygdalae of 3 out 10 patients who underwent curative stereotactic surgery for severe mental retardation with aggressive behavior and/or paranoic schizophrenia. Of these, 6 were also tested for the presence of CMV DNA sequences with negative results. Biopsy specimens from nc. amygdalae of another 7 psychotic patients were cultured in vitro but no virus was isolated.