Author Correction: A population of luminous accreting black holes with hidden mergers.

In this Letter, the spelling of author Benny Trakhtenbrot was corrected; the affiliation for author Sylvain Veilleux was amended; and a new ref. 9 was added to the Abstract with subsequent references renumbered; these errors have been corrected online.

A population of luminous accreting black holes with hidden mergers.

Major galaxy mergers are thought to play an important part in fuelling the growth of supermassive black holes1. However, observational support for this hypothesis is mixed, with some studies showing a correlation between merging galaxies and luminous quasars2,3 and others showing no such association4,5. Recent observations have shown that a black hole is likely to become heavily obscured behind merger-driven gas and dust, even in the early stages of the merger, when the galaxies are well separated6-8 (5 to 40 kiloparsecs). Merger simulations further suggest that such obscuration and black-hole accretion peaks in the final merger stage, when the two galactic nuclei are closely separated9 (less than 3 kiloparsecs). Resolving this final stage requires a combination of high-spatial-resolution infrared imaging and high-sensitivity hard-X-ray observations to detect highly obscured sources. However, large numbers of obscured luminous accreting supermassive black holes have been recently detected nearby (distances below 250 megaparsecs) in X-ray observations10. Here we report high-resolution infrared observations of hard-X-ray-selected black holes and the discovery of obscured nuclear mergers, the parent populations of supermassive-black-hole mergers. We find that obscured luminous black holes (bolometric luminosity higher than 2 × 1044 ergs per second) show a significant (P < 0.001) excess of late-stage nuclear mergers (17.6 per cent) compared to a sample of inactive galaxies with matching stellar masses and star formation rates (1.1 per cent), in agreement with theoretical predictions. Using hydrodynamic simulations, we confirm that the excess of nuclear mergers is indeed strongest for gas-rich major-merger hosts of obscured luminous black holes in this final stage.

The close environments of accreting massive black holes are shaped by radiative feedback.

The majority of the accreting supermassive black holes in the Universe are obscured by large columns of gas and dust. The location and evolution of this obscuring material have been the subject of intense research in the past decades, and are still debated. A decrease in the covering factor of the circumnuclear material with increasing accretion rates has been found by studies across the electromagnetic spectrum. The origin of this trend may be driven by the increase in the inner radius of the obscuring material with incident luminosity, which arises from the sublimation of dust; by the gravitational potential of the black hole; by radiative feedback; or by the interplay between outflows and inflows. However, the lack of a large, unbiased and complete sample of accreting black holes, with reliable information on gas column density, luminosity and mass, has left the main physical mechanism that regulates obscuration unclear. Here we report a systematic multi-wavelength survey of hard-X-ray-selected black holes that reveals that radiative feedback on dusty gas is the main physical mechanism that regulates the distribution of the circumnuclear material. Our results imply that the bulk of the obscuring dust and gas is located within a few to tens of parsecs of the accreting supermassive black hole (within the sphere of influence of the black hole), and that it can be swept away even at low radiative output rates. The main physical driver of the differences between obscured and unobscured accreting black holes is therefore their mass-normalized accretion rate.

Novel probabilistic model of core vitreous traction using microsurgical vitrectomy tools.

PURPOSE: Traction exerted on the vitreous base during vitrectomy poses a risk for retinal tears. We aimed to quantify core vitreous traction during vitrectomy using spring return and pneumatic cutters. METHODS: Juvenile porcine vitreous was vacuum held in a vitreous bath while traction was measured using precision force gauge during vitrectomy. The parameters included were aspiration rate, cut-rate, cutter size, and machine types. RESULTS: An empirical probabilistic model was developed. The traction was proportional to the aspiration rate but insignificantly dependent on the cut-rate. The traction probability was inversely proportional to the exponential function of the traction (p < 0.05). The traction was < 0.003 N for 99% of the time using either 23- or 25-gauge cutters. CONCLUSION: The tractions measured were considered similar to the causative forces of an iatrogenic retinal tear during a pars plana vitrectomy. The results provide a safety reference matrix of instrumental parameters during vitrectomy.

Application of subretinal fluid to close refractory full thickness macular holes: treatment strategies and primary outcome: APOSTEL study.

INTRODUCTION: Persisting macular holes (PMH) after surgical release of any epiretinal traction of the vitreous and adjacent membrane may rely on secondary firm adhesions between the retracted retina and adjacent retinal pigment epithelium. Secondary application of subretinal (SR)-fluid may release these adhesions followed by an anatomical closure. METHODS: Twelve surgeons applied in a consecutive case series SR-fluid in 41 eyes with PMH and reported retrospectively their initial surgical, anatomical and functional experience with this approach. RESULTS: The mean duration of the MH prior to SR-fluid application was 17 months (6-96 months). The mean age of the patients at the time of surgery was 72 years (54-88). The mean preoperative aperture diameter of the opening was 1212 µm (239-4344 µm), base diameter 649 µm (SD 320 µm). The mean preoperative BCVA prior to surgery was 0.1 (0.01-0.3). All patients (41/41) complained about reduced BCVA and a significant central scotoma (negative scotoma) in their central field of vision. The secondary closure rate for our PMH was 85.36% (35 out of 41 eyes) at 6 weeks after surgery. The postoperative BCVA improved to 0.22 (0.02-0.5). The application of SR-fluid was not associated with major intraoperative adverse effects. CONCLUSION: Remaining SR-adhesions may inhibit PMH closure. Their release by application of SR-fluid will lead to a fast and immediate anatomical closure in many cases without serious adverse events.

The predictability of ocriplasmin treatment effects: is there consensus among retinal experts? Results from the EXPORT study.

PURPOSE: To evaluate the agreement and predictability of ocriplasmin treatment effects among retinal experts (raters) by assessment of retinal imaging data of eyes treated for vitreomacular traction in nine different centers in Germany and Austria. METHODS: Retrospective cohort study. Combined confocal near-infrared scanning laser ophthalmoscopy and spectral-domain optical coherence tomography images (Spectralis® device, Heidelberg Engineering GmbH, Germany) from 136 eyes of 135 subjects were reviewed by 14 raters using an internet-based grading database and a standardized questionnaire. In addition to the images taken within 2 days prior to treatment, age, gender, and lens status were disclosed to the raters. Treatment success was defined as a complete cleavage of the posterior vitreous cortex at day 28±5. Main outcome was the agreement and predictability among raters for assessment of treatment success. RESULTS: Raters generally accepted starting ocriplasmin treatment (chance for treatment success ≥ 1%) in 22.4 to 69.1% (median 53.2%) of eyes (moderate intra- and interrater agreements with kappa-values of 0.6 and 0.48). The likelihood for a high potential treatment success (equal or higher than 25%) was judged by the raters in 43.4% to 86.0% (median 62.6%) of eyes (moderate intra- and fair interrater agreements with kappa-values of 0.56 and 0.22). Allocating eyes for high potential treatment success overall increased the odds by 3.07, with odds ratios of single raters up to 4.06 to 6.16. CONCLUSIONS: These results underscore the importance of training health care providers in the evaluation of retinal imaging data and also to define characteristic morphological features better in the presence of vitreoretinal interface diseases. The better results of single raters in the predictability of treatment success by the allocation of eyes in the high-potential group indicates the high relevance of the meticulous analysis of retinal images.

VITRECTOMY FOR PERSISTENT MACULAR HOLES FOLLOWING OCRIPLASMIN INJECTION: A Comparative Multicenter Study.

PURPOSE: To determine functional and anatomical outcomes of pars plana vitrectomy for persistent full-thickness macular hole (MH) after intravitreal injection of ocriplasmin. METHODS: This is a multicenter retrospective interventional study of 37 eyes of 37 patients who underwent pars plana vitrectomy with internal limiting membrane peeling for persistent MH after ocriplasmin treatment between December 2013 and December 2015 and comparison with 35 eyes of 35 patients who were offered ocriplasmin injection but underwent pars plana vitrectomy alone without pharmacologic vitreolysis before surgery. In addition, 24 matched pairs (MH diameter at baseline ±5 µm) were analyzed. Clinical data such as visual acuity, intraoperative characteristics, and spectral domain optical coherence tomography images were reviewed. Main outcome measures were visual acuity and MH closure rate. RESULTS: After a mean follow-up period of 9 months, postoperative mean visual acuity showed no significant differences between ocriplasmin-treated eyes (logarithm of minimum angle of resolution 0.37 ± 0.26, Snellen 20/47) and eyes without ocriplasmin treatment (logarithm of minimum angle of resolution 0.39 ± 0.25; Snellen 20/49) (P > 0.9). After ocriplasmin injection, mean MH diameter enlarged from 217 ± 102 µm to 384 ± 239 µm (P < 0.001). Matched-pair analysis revealed no difference in gain of visual acuity between the first visit and the last follow-up (P = 0.29). Macular hole closure was observed in similar proportion in ocriplasmin-treated eyes (97%) and vitrectomy-only eyes (94%) (P > 0.5). CONLCUSION: Eyes with persistent MH after ocriplasmin injection showed significant visual improvement after pars plana vitrectomy. Matched-pair analysis revealed no statistical differences in functional and anatomical postoperative results comparing with eyes of similar MH diameter that proceeded directly to surgery without ocriplasmin pretreatment.

IMPACT OF VITREORETINAL INTERFACE ARCHITECTURE ON SUCCESSFUL VITREOMACULAR TRACTION RESOLUTION IN EYES SCHEDULED FOR INTRAVITREAL OCRIPLASMIN THERAPY.

PURPOSE: To evaluate the impact of the vitreoretinal interface architecture, in specific the angle between the posterior vitreous cortex and the internal limiting membrane, on vitreomacular traction (VMT) resolution in eyes treated with intravitreally injected ocriplasmin (Jetrea). METHODS: Retrospective, multicenter cohort study and exploratory data analysis. Spectral domain optical coherence tomography assessments were performed before scheduled ocriplasmin injections. General (age and sex) as well as ocular variables (lens status, presence of epiretinal membrane formations, horizontal diameter of VMT, central retinal thickness, and in particular various prespecified angles between the posterior vitreous cortex and internal limiting membrane) were analyzed to evaluate their impact on successful VMT resolution. RESULTS: Fifty-nine eyes of 59 patients were included. Univariate analysis of age (odds ratio [OR]: 0.881; 95% CI: [0.812-0.955]; P = 0.0022) and lens status (OR: 11.03; 95% CI: [2.23-54.57]; P = 0.0033) had a significant impact on successful VMT resolution, whereas sex (OR: 0.668; 95% CI: [0.126-2.065]; P = 0.4906), epiretinal membrane formation (OR: 0.581; 95% CI: [0.168-2.006]; P = 0.3903), horizontal diameter of VMT (OR: 0.99930; 95% CI: [0.99825-1.00035]; P = 0.1886), and central retinal thickness (OR: 0.9985; 95% CI: [0.9934-1.00436]; P = 0.56) failed. The angle at 500 µm apart from the fovea centralis, irrespective if measured nasally (OR: 1.135; 95% CI: [1.013-1.272]; P = 0.0289) or temporally (OR: 1.099; 95% CI: [1.001-1.208]; P = 0.0485), showed a significant correlation with VMT resolution. CONCLUSION: The angle between the posterior vitreous cortex and the internal limiting membrane 500 µm apart from the fovea centralis correlates with VMT resolution and may be a clinically useful marker for selection of patients to be treated with ocriplasmin. This observation needs to be proven in a prospective confirmatory investigation.

Proteomics of vitreous in neovascular age-related macular degeneration.

Neovascular age-related macular degeneration (nAMD) has been described as a predominantly inflammatory and proangiogenic retino-choroidal disease. Vitreous humor (VH) is the adjacent and accessible compartment which, due to the vicinity to the retina, might best represent changes of protein-based mediators of nAMD. The aim of this clinical-experimental study was to analyze the nAMD associated VH proteome of previously untreated patients whilst taking different groups of nAMD into account, based on their clinical presentation (clinical diagnosis groups). Electrophoresis coupled online to mass spectrometry (CE-MS) as well as liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) were used to analyze VH of 108 nAMD patients and 24 controls with idiopathic floaters. A total of 101 different proteins with at least two unique peptides could be identified. Using a stringent statistical analysis with implementation of the closed test principle, we were able to identify four proteins that may be involved in the pathophysiology of nAMD: Clusterin, opticin, pigment epithelium-derived factor and prostaglandin-H2 d-isomerase. Using independent samples, ROC-Area under the curve was determined proving the validity of the results: Clusterin 0.747, opticin 0.656, pigment epithelium-derived factor 0.514, prostaglandin-H2 d-isomerase 0.712. In addition, validation through ELISA measurements was performed. The identified proteins may serve as potential biomarkers or even targets of therapy for nAMD.

Vancomycin in infusion during vitrectomy in surgical treatment of acute postoperative and posttraumatic endophthalmitis.

BACKGROUND: Endophthalmitis is potentially devastating intraocular inflammation following eye trauma or surgery. We describe the visual outcomes and causative pathogens in acute bacterial postoperative and posttraumatic endophthalmitis treated with immediate pars plana vitrectomy (PPV) with Vancomycin dissolved in the infusion fluid. METHODS: Clinical records of consecutive 30 patients with postoperative endophthalmitis and 15 patients with posttraumatic endophthalmitis were evaluated. Vancomycin was administered constantly in the infusion fluid at the time of complete PPV. Cultures were prepared from anterior chamber paracentesis. The mean follow-up period was 13 months. RESULTS: The visual acuities were improved in 38 cases (84 %) and remained stable in seven cases (16 %). Median post-PPV visual acuity was 1.0 logMAR in a group with postoperative endophthalmitis and 1.3 logMAR in a group with posttraumatic endophthalmitis (p < 0.05). Twenty cases (44 %) were culture-positive (Staphylococcus, Streptococcus, Enterococcus and Bacillus spp). CONCLUSIONS: Early PPV with Vanomycin in infusion leads to vision improvement in patients with both posttraumatic and postoperative endophthalmitis. In our series of 45 cases culture was positive only in half of the cases.

Subretinal implantation of a monolayer of human embryonic stem cell-derived retinal pigment epithelium: a feasibility and safety study in Yucatán minipigs.

PURPOSE: A subretinal implant termed CPCB-RPE1 is currently being developed to surgically replace dystrophic RPE in patients with dry age-related macular degeneration (AMD) and severe vision loss. CPCB-RPE1 is composed of a terminally differentiated, polarized human embryonic stem cell-derived RPE (hESC-RPE) monolayer pre-grown on a biocompatible, mesh-supported submicron parylene C membrane. The objective of the present delivery study was to assess the feasibility and 1-month safety of CPCB-RPE1 implantation in Yucatán minipigs, whose eyes are similar to human eyes in size and gross retinal anatomy. METHODS: This was a prospective, partially blinded, randomized study in 14 normal-sighted female Yucatán minipigs (aged 2 months, weighing 24-35 kg). Surgeons were blinded to the randomization codes and postoperative and post-mortem assessments were performed in a blinded manner. Eleven minipigs received CPCB-RPE1 while three control minipigs underwent sham surgery that generated subretinal blebs. All animals except two sham controls received combined local (Ozurdex™ dexamethasone intravitreal implant) and systemic (tacrolimus) immunosuppression or local immunosuppression alone. Correct placement of the CPCB-RPE1 implant was assessed by in vivo optical coherence tomography and post-mortem histology. hESC-RPE cells were identified using immunohistochemistry staining for TRA-1-85 (a human marker) and RPE65 (an RPE marker). As the study results of primary interest were nonnumerical no statistical analysis or tests were conducted. RESULTS: CPCB-RPE1 implants were reliably placed, without implant breakage, in the subretinal space of the minipig eye using surgical techniques similar to those that would be used in humans. Histologically, hESC-RPE cells were found to survive as an intact monolayer for 1 month based on immunohistochemistry staining for TRA-1-85 and RPE65. CONCLUSIONS: Although inconclusive regarding the necessity or benefit of systemic or local immunosuppression, our study demonstrates the feasibility and safety of CPCB-RPE1 subretinal implantation in a comparable animal model and provides an encouraging starting point for human studies.

INTRAOCULAR PRESSURE CHANGES DURING VITRECTOMY USING CONSTELLATION VISION SYSTEM'S INTRAOCULAR PRESSURE CONTROL FEATURE.

PURPOSE: To evaluate intraocular pressure (IOP) changes during experimental vitrectomy and the efficacy of Constellation Vision System's IOP control (IOPc) feature in reestablishing baseline pressure. METHODS: Using a pressure transducer in freshly enucleated porcine eyes, a broad range of parameters (baseline pressures, aspiration levels, and cut rates) were tested with 23- and 25-gauge probes and IOPc turned ON versus OFF. RESULTS: IOPc turned ON was significantly more effective than IOPc turned OFF in controlling IOP drop and stabilizing pressure during vitrectomy using a wide range of baseline pressures (20-70 mmHg). The 23-gauge system consistently presented a reduced drop from baseline compared with the 25-gauge system. The overall average drop for the 23- and 25-gauge systems was 12.79 mmHg and 21.17 mmHg, respectively. Both gauge sizes reestablished baseline pressure approximately 1.6 seconds after the initial pressure drop generated at the beginning of aspiration. A peak of IOP (overshooting) was observed when the pressure was returning to baseline using both 23- and 25-gauge systems. CONCLUSION: Using IOPc feature turned ON, 23- and 25-gauge probes were effective in reestablishing and sustaining baseline infusion pressures, although 23-gauge probes showed less IOP fluctuation than did 25-gauge probes.

LYSOPHOSPHATIDIC ACIDS AND AUTOTAXIN IN RETINAL VEIN OCCLUSION.

PURPOSE: To analyze the levels of lysophosphatidic acids (LPAs) and autotaxin (ATX) in undiluted vitreous of untreated patients with retinal vein occlusion (RVO). METHODS: Sixty-four vitreous samples (40 RVO, 24 controls with idiopathic floaters) were analyzed in this retrospective case series using LC/MS for LPAs 16:0, 18:0, 18:1, 20:4, and ELISA kits or Luminex technology for ATX, angiopoetin-1 (ANG-1), interleukin-6 (IL-6), interleukin-7 (IL-7), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), pigment epithelium-derived factor (PEDF), and vascular endothelial growth factor (VEGF). LPA and ATX levels were correlated with the visual acuity, central macular thickness (CMT), average retinal thickness (AvT), vitreal cytokine levels and with each other. RESULTS: Levels of every LPA species tested and ATX were significantly increased in the vitreous fluid from all patients with RVO (total LPAs: 968.0 ± 842.3 nM; ATX: 2.5 ± 1.02 nM) compared with controls (total LPAs: 225.2 ± 292.8 nM, P < 0.0001; ATX: 1.9 ± 1.00 nM, P = 0.005). There were strong positive correlations between the vitreal levels of IL-6, IL-8, MCP-1, VEGF and LPAs. CONCLUSION: Levels of LPAs and ATX were positively correlated with proinflammatory cytokines and VEGF and might thus play an important role in the development of macular edema secondary to RVO.

Current treatment modalities in diabetic macular edema.

Diabetic macular edema is the major cause of vision impairment in the diabetic population. Its treatment requires a multidisciplinary approach and the use of both systemic and local therapies. Current management includes the vascular endothelial growth factor inhibitors and steroids administered as intravitreal injections, as well as laser therapy and surgical treatment. Treatment modalities in diabetic macular edema have changed in recent years, after the introduction of vascular endothelial growth factor inhibitors, which are gradually replacing laser photocoagulation. All anti-VEGF agents tested so far showed efficacy in the treatment of diabetic macular edema. Due to structural differences, the therapeutic efficacy of different anti-VEGF products varies. According to recent results, 2,0 mg of aflibercept is more effective than 0,3 mg of ranibizumab in patients with lower visual acuity at baseline. Additionally, its superiority was shown in reducing the number of required macular laser photocoagulation procedures. This article provides a comprehensive overview of available therapeutic modalities based on laser photocoagulation, anti-VEGF agents, steroid injections or surgical interventions, and discusses their efficacy in patients with diabetic macular edema.

Intermediate and near visual acuity of an aspheric, bifocal, diffractive multifocal intraocular lens with +3.25 D near addition.

PURPOSE: To evaluate the clinical outcomes after cataract surgery with implantation of a new diffractive multifocal intraocular lens with a lower near addition. METHODS: A prospective multicenter clinical study including 44 eyes of 44 patients (age range: 43 to 82 years) that underwent cataract surgery with implantation of the Tecnis ZLB00 multifocal intraocular lens (Abbott Medical Optics, Santa Ana, CA). Changes in uncorrected and corrected distance, intermediate, and near visual acuity, and manifest refraction were evaluated during a 3-month follow-up. Additionally, patients were asked about photic phenomena and spectacle dependence. RESULTS: Postoperative spherical equivalent was within 0.50 and ± 1.00 diopters of emmetropia in 91.2% and 100% of eyes, respectively. Postoperative monocular uncorrected distance, near, and intermediate visual acuities were 0.10 logMAR (20/25 Snellen) or better in 82.5%, 86.5%, and 68.8% of eyes, respectively. All eyes achieved monocular corrected distance and near visual acuity of 0.10 logMAR (20/25 Snellen) or better. All patients reported to be satisfied with the outcomes of the surgery. Only 6 patients (13.6%) required the use of spectacles for some daily activities postoperatively, and 8 patients (18.2%) reported mild perception of halos. CONCLUSIONS: The introduction of low addition multifocal intraocular lenses follows a trend to increase intermediate visual acuity. Still, a near addition of +3.25 diopters reached satisfying near results and led to high patient satisfaction.

Clinical Outcomes After Implantation of a Trifocal Toric Intraocular Lens.

PURPOSE: To evaluate the visual, refractive, and contrast sensitivity outcomes, as well as the level of photic phenomena, after cataract surgery with implantation of a trifocal diffractive toric intraocular lens (IOL). METHODS: This prospective study included 56 eyes with corneal astigmatism of 1.00 diopters (D) or greater of 28 patients (age: 23 to 78 years) undergoing cataract surgery with implantation of the trifocal toric IOL AT LISA tri toric 939MP (Carl Zeiss Meditec, Jena, Germany). Monocular and binocular visual outcomes, refractive changes, contrast sensitivity, and photic phenomena perception (Halo & Glare Simulator; Eyeland-Design Network GmbH, Vreden, Germany) were evaluated at 3 months postoperatively. RESULTS: Mean 3-month postoperative monocular uncorrected distance (UDVA), intermediate (UIVA), and near (UNVA) visual acuities were 0.13±0.15, 0.08±0.15, and 0.13±0.18 logMAR, respectively. Binocular postoperative CDVA, DCIVA, and DCNVA values were 0.10 logMAR or better in all cases. A total of 88.2%, 88.2%, and 95.5% of eyes achieved binocular UDVA, UIVA, and UNVA values of 0.20 logMAR or better, respectively. Postoperative refractive cylinder was 0.50 D or less and 1.00 D or less in 78.6% and 98.2% of eyes, respectively. Photopic contrast sensitivity was significantly better than mesopic values for the spatial frequencies of 6 (P=.007), 12 (P=.005), and 18 cycles/degree (P=.011). Mean size and intensity of halos were 50.67±15.69 and 54.89±17.86, respectively. Mean glare size and intensity were 39.67±3.51 and 44.67±15.01, respectively. CONCLUSIONS: The evaluated trifocal diffractive toric IOL provides an effective restoration of the distance, intermediate, and near vision after cataract surgery with good levels of visual quality and minimal photic phenomena.

Surgical treatment of open globe trauma complicated with the presence of an intraocular foreign body.

BACKGROUND: Open globe injuries complicated with the presence of an intraocular foreign body constitute a vision threatening condition. PURPOSE: To present the results of pars plana vitrectomy in patients with intraocular foreign body. MATERIAL AND METHODS: Medical records of 22 patients were analyzed. Retrospective analysis of data included visual acuity, age, gender and type of injury. RESULTS: All patients were men and the mean age was 37 years. All injuries occurred while working with a hammer. All patients were treated with pars plana vitrectomy combined with intraocular foreign body removal and internal limiting membrane peeling. The visual acuities improved in 9 cases (41%), in 13 cases (59%) the deterioration of visual acuity was observed, no eye was enucleated. In 14 eyes pars plana vitrectomy was combined with lens removal, in 14 eyes silicone oil was used as a tamponade. CONCLUSIONS: Surgical intervention with pars plana vitrectomy combined with intraocular foreign body removal and cataract extraction may preserve severely traumatized eyes and maintain or even improve vision. ocular trauma, vitrectomy, intraocular foreign body.

Relationship between the area of isopters and Vigabatrin dosage during two years of observation.

BACKGROUND: The aim of the study was to evaluate the relationship between the area of isopters obtained using semi-automated kinetic perimetry (SKP) and Vigabatrin dosage in epilepsy patients with pretreatment baseline examination during 2-years of the follow-up. METHODS: 29 epilepsy patients were included into the study, but 15 individuals were excluded due to cognitive impairment, intracranial pathologies or eye diseases. Finally, 14 patients were examined with SKP before VGB treatment and after 6, 12, 18, and 24 months. Reaction time (RT)-corrected areas of three isopters (III4e, I4e and I2e) were measured for each of five examinations and compared intra-individually during 2-years period. Additionally, six epilepsy patients on other antiepileptic drugs were examined five times with SKP as a control. RESULTS: There was a significant decrease of I2e, I4e and III4e isopters' area during the follow-up of two years. Correlation was found between the I2e isopter's area and both cumulative dose and mean daily dose of VGB. With increasing RT, there was decreasing of all isopters' area in patients receiving VGB. In epilepsy patients who were not receiving VGB, there were no significance differences in isopters' area during follow-up. CONCLUSION: There was attenuation of area of III4e, I4e and I2e isopters obtained with SKP during a period of 2 years. RT, the cumulative dose and the mean daily dose of VGB influenced isopters' area obtained with SKP.

Intravitreal functional plasminogen in eyes with branch retinal vein occlusion.

PURPOSE: To evaluate whether intravitreal functional plasminogen is elevated in eyes with branch retinal vein occlusion (BRVO) and to discover whether intravitreal plasminogen activities are correlated with the extent of blood-retina barrier (BRB) breakdown. METHODS: Our study is a prospective case series of 20 consecutive patients with BRVO and 10 consecutive patients serving as controls. Vitreous taps were extracted from the central vitreous body and plasminogen was functionally determined in an innovative, ultrasensitive p-nitroanilide reaction after activation with streptokinase (100% of normal, %N = functional plasminogen in pooled normal citrated plasma). Intravitreal VEGF levels were assayed to estimate BRB breakdown. RESULTS: Intravitreal functional plasminogen was detected in all analyzed samples (n = 30) and mean (±SD) plasminogen activities were found to be 0.97 ± 1.06%N (range: 0.03-3.9%N). Patients suffering from BRVO exhibited significantly higher intravitreal plasminogen (1.35 ± 1.11%N) in comparison with controls (0.20 ± 0.21%N, p < 0.001). Intravitreal VEGF concentrations in the BRVO group (576 ± 547 pg/ml) were significantly higher than these in controls (111 ± 120 pg/ml, p = 0.003). There was a significant correlation between intravitreal functional plasminogen and intravitreal VEGF levels (r = 0.519, p = 0.003). CONCLUSIONS: Intravitreal functional plasminogen is significantly elevated in eyes suffering from BRVO and correlates with the extent of BRB breakdown. The induction of posterior vitreous detachment by using intravitreally administered recombinant tissue plasminogen activator (enzymatic vitreolysis) should be explored in further investigations.

Intravitreal functional plasminogen is elevated in central retinal vein occlusion.

PURPOSE: To detect intravitreal functional plasminogen in vitreous samples of patients with recent onset of central retinal vein occlusion (CRVO) and to demonstrate significantly higher intravitreal plasminogen in CRVO patients in comparison to controls. METHODS: Prospective clinical case series of 13 consecutive patients with recent onset of CRVO scheduled for core pars plana vitrectomy and 10 consecutive patients undergoing standard pars plana vitrectomy for routine macular surgery or vitreal floater removal. In all 23 cases, vitreous taps were extracted from the central vitreous body, and plasminogen was functionally determined in a new ultrasensitive p-nitroanilide reaction after activation with streptokinase (100% of normal, %N = functional plasminogen in pooled normal citrated plasma). RESULTS: Plasminogen was detected in all analyzed samples (n = 23), and mean plasminogen was revealed to be 1.33 ± 1.73% (mean ± SD), with a range of 0.03-7.8%N. Patients with recent onset of CRVO exhibited significantly higher intravitreal plasminogen (2.19 ± 1.89%N) in comparison to controls (0.20 ± 0.21%N; p < 0.001, Mann-Whitney U test). CONCLUSION: Due to significantly increased intravitreal plasminogen in patients with recent onset of CRVO, intravitreally administered tissue plasminogen activator might be an option to induce posterior vitreous detachment (enzymatic vitreolysis) in CRVO patients.