Randomised controlled trial on robot-assisted versus manual surgery for pucker peeling.

BACKGROUND: The aim was to explore the feasibility and safety of performing common surgical steps in epiretinal membrane (ERM) peeling using the Preceyes Surgical System (PSS). METHODS: In a tertiary centre, 15 pseudophakic patients with an idiopathic ERM were randomised to robot-assistance or manual surgery in a 2:1 ratio. In the robot-assisted group, the following steps were performed using PSS: (1) staining the internal limiting membrane (ILM), (2) removal of the dye, (3) creating an ILM flap, (4) completing the peeling, (5) holding a light pipe and (6) fluid-air exchange. Primary outcome measures were feasibility and safety. Secondary outcome measures were duration, best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Moreover, the distance travelled by the instrument during peeling was assessed using motion tracking software. RESULTS: All steps performed with PSS were feasible with no clinical adverse events or complications. The surgical time was longer in the robot-assisted group (mean 56 min, SD = 12 vs. 24 min, SD = 5). During the study, the duration of robot-assisted surgeries decreased from 72 to 46 min. The distance travelled by the forceps was shorter in the robot-assisted group (mean 403 mm, SD = 186 vs. 550 mm, SD = 134). BCVA and CRT improved equally in both groups. CONCLUSIONS: This is the world's first randomised controlled trial on robotic surgery for ERM. Although more time-consuming, we found that several surgical steps were feasible with assistance of the PSS.

PROPHYLACTIC LASER TREATMENT TO DECREASE THE INCIDENCE OF RETINAL DETACHMENT IN FELLOW EYES OF IDIOPATHIC GIANT RETINAL TEARS.

PURPOSE: To evaluate the effectiveness of prophylactic 360° laser treatment in the fellow eye of patients with unilateral idiopathic giant retinal tear (GRT) to prevent the occurrence of a (macula-off) retinal detachment. METHODS: We conducted a retrospective, nonrandomized case-control study. Clinical data of consecutive patients, undergoing surgery for idiopathic GRT, between 2003 and 2015 were analyzed. The data collected included GRT, retinal detachment, and RTs in the fellow eye. RESULTS: We included 129 patients who underwent surgery for an idiopathic GRT, with a mean follow-up period of 107 months. In the observation group, a retinal detachment developed in the fellow eye in 22/51 patients (43.1%), leading to a macula-off detachment in 9/51 patients (17.6%). By contrast, in the prophylactic 360° laser group, only 10/78 (12.8%) patients developed a retinal detachment, leading to a macula-off detachment in 1/78 patient (1.3%). This difference was statistically significant. CONCLUSION: This study suggests that prophylactic 360° laser treatment in the fellow eye of patients with an idiopathic GRT decreased the incidence of retinal detachment, lowering the high risk of visual loss due to a macula-off retinal detachment.

STRICT POSTURING WITH OR WITHOUT BILATERAL PATCHING FOR POSTERIOR VITREOUS DETACHMENT-RELATED VITREOUS HEMORRHAGE.

PURPOSE: To determine whether bilateral patching with posturing is superior to posturing alone in visualizing the superior retina in suspected posterior vitreous detachment (PVD)-related vitreous hemorrhage (VH). METHODS: Prospective randomized controlled trial: 80 patients with fundus-obscuring VH due to suspected retinal tear were randomized to strict posturing and bilateral patching overnight (Treatment A, 40 patients) or posturing (Treatment B, 40 patients). PRIMARY OUTCOME: Visualization of ≥4 clock hours superior retina. SECONDARY OUTCOME MEASURES: laser treatment, vitrectomy rate, and retinal detachment within 12 months. RESULTS: Intention-to-treat analysis: In 38/40 (95%) with Treatment A and 32/40 (80%) with Treatment B, the confirmed diagnosis was PVD-related VH. Visibility of the superior retina for all patients: 29/40 (73%) after Treatment A and 21/40 (53%) after Treatment B (P = 0.07). Subgroup analysis for confirmed PVD-related VH; visibility of the superior retina: 29/38 (76%) after Treatment A and 15/32 (47%) after Treatment B (P = 0.01). In subgroup analysis, vitrectomy rate within 12 months was 61% (Treatment A) and 53% (Treatment B) (P = 0.63). Retinal detachment: eight patients after each treatment. CONCLUSION: In patients with suspected PVD-related VH, overnight bilateral patching was not superior to posturing alone in superior retina visualization, but in a post-hoc analysis of patients with confirmed PVD-related VH, bilateral patching was superior.

Thrombin Generation in Vitreous and Subretinal Fluid of Patients with Retinal Detachment.

PURPOSE: To measure prothrombin fragments (F1+2) and thrombin-antithrombin complex (TAT) in vitreous and subretinal fluid (SRF) of rhegmatogenous retinal detachment (RRD) patients and to validate and further specify our earlier finding of increased thrombin activity in patients with proliferative vitreoretinopathy (PVR). METHODS: F1+2 and TAT were measured in 31 vitreous and 16 SRF samples using the Enzygnost® immunoassays. RESULTS: We found significant levels of F1+2 and TAT in the vitreous of all patients with RRD compared to patients with macular hole or macular pucker. However, there was no significant difference between patients who would develop PVR in the future, had established PVR, and patients with uncomplicated RRD both in vitreous concentrations of F1+2 (Kruskal-Wallis p = 0.963) and TAT (p = 0.516). CONCLUSION: The analysis of F1+2 and TAT confirmed significant thrombin generation in both vitreous and SRF of patients with RRD. An imbalance between the thrombin regulation mechanisms TAT and α2-macroglobulin possibly explains the difference from our previous findings.

Preoperative Posturing of Patients with Macula-On Retinal Detachment Reduces Progression Toward the Fovea.

PURPOSE: Traditionally, preoperative posturing consisting of bed rest and positioning is prescribed to patients with macula-on retinal detachment (RD) to prevent RD progression and detachment of the fovea. Execution of such advice can be cumbersome and expensive. This study aimed to investigate if preoperative posturing affects the progression of RD. DESIGN: Prospective cohort study. PARTICIPANTS: Ninety-eight patients with macula-on RD were included. Inclusion criteria were volume optical coherence tomography (OCT) scans could be obtained with sufficient quality; and the smallest distance from the fovea to the detachment border was 1.25 mm or more. METHODS: Patients were admitted to the ward for bed rest in anticipation of surgery and were positioned on the side where the RD was mainly located. At baseline and before and after each interruption for meals or toilet visits, a 37°×45° OCT volume scan was performed using a wide-angle Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). The distance between the nearest point of the RD border and fovea was measured using a custom-built measuring tool. MAIN OUTCOME MEASURES: The RD border displacement and the average RD border displacement velocity moving toward (negative) or away (positive) from the fovea were determined for intervals of posturing and interruptions. RESULTS: The median duration of intervals of posturing was 3.0 hours (interquartile range [IQR], 1.8-14.0 hours; n = 202) and of interruptions 0.37 hours (IQR, 0.26-0.50 hours; n = 197). The median RD border displacement was 2 µm (IQR, -65 to +251 µm) during posturing and -61 µm (IQR, -140 to 0 µm) during interruptions, a statistically significant difference (P < 0.001, Mann-Whitney U test). The median RD border displacement velocity was +1 µm/hour (IQR, -21 to +49 µm/hour) during posturing and -149 µm/hour (IQR, -406 to +1 µm/hour) during interruptions, a statistically significant difference (P < 0.001). CONCLUSIONS: By making use of usual interruptions of preoperative posturing we were able to show, in a prospective and ethically acceptable manner, that RD stabilizes during posturing and progresses during interruptions in patients with macula-on RD. Preoperative posturing is effective in reducing progression of RD.

INTRAVITREAL VERSUS SUBRETINAL ADMINISTRATION OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR COMBINED WITH GAS FOR ACUTE SUBMACULAR HEMORRHAGES DUE TO AGE-RELATED MACULAR DEGENERATION: An Exploratory Prospective Study.

PURPOSE: Current management of submacular hemorrhage (SMH) favors vitrectomy and gas with subretinal administration of recombinant tissue plasminogen activator (rtPA) over mere intravitreal rtPA injections and gas. In this study, we aimed to compare the effectiveness of both treatment modalities to displace submacular blood. METHODS: Twenty-four patients with SMH secondary to age-related macular degeneration were included. The SMH had to exist ≤14 days at time of surgery and SMH thickness had to be between 250 µm and 1,250 µm. Patients were randomized to either intravitreal injections of rtPA, perfluoropropane (C3F8) gas, and bevacizumab (n = 12) or vitrectomy with subretinal rtPA administration, intravitreal C3F8 gas, and bevacizumab (n = 12). The SMH volume change was measured on spectral domain optical coherence tomography postoperatively within a 2.5-mm cylinder centered at the fovea. RESULTS: Median relative volume reduction of subretinal blood at 6 weeks postoperatively was 97% (95% confidence interval: 91-99%) in the intravitreal rtPA group and 100% (95-100%) in the subretinal rtPA group and did not differ significantly between groups (P = 0.56). CONCLUSION: Both treatment modalities effectively displaced SMH in this exploratory clinical trial. To more definitely study the noninferiority of intravitreal rtPA with gas to subretinal rtPA, vitrectomy with gas, a larger clinical trial would be necessary.

Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability.

Antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used as antiinflammatory drugs, but side effects include retinopathy and vision loss. The objective of this study was to examine the effect of CQ and HCQ on the barrier integrity of retinal pigment epithelial (RPE) cell monolayers in vitro. Permeability of ARPE-19 cell monolayers was determined using Fluorescein isothiocyanate (FITC)-labeled dextran. The influence of CQ and HCQ on cell death and the expression tight junction molecules was examined. CQ and HCQ significantly increased ARPE-19 monolayer permeability after 3 and 18 h, respectively, and enhanced mRNA levels for claudin-1 and occludin. Cytotoxicity was only observed after 18 h exposure. Thus, CQ and HCQ rapidly enhance RPE barrier permeability in vitro, independent of cytotoxicity or loss of zonula occludens-1, claudin-1, and occludin expression. Our findings suggest that CQ/HCQ-induced permeability of the RPE layer may contribute to blood-retinal barrier breakdown in case of CQ/HCQ-induced retinopathy.

Prospective, Randomized Intervention Study Comparing Retinal Pigment Epithelium-Choroid Graft Surgery and Anti-VEGF Therapy in Patients with Exudative Age-Related Macular Degeneration.

PURPOSE: To investigate whether patients with exudative age-related macular degeneration and a submacular hemorrhage, retinal pigment epithelium (RPE) tear or nonresponders to anti-vascular endothelial growth factor (VEGF) benefit more from a free RPE-choroid graft transplantation surgery than from (continuation of) anti-VEGF treatment. PROCEDURES: A total of 20 patients were included in this prospective, international, multicenter, randomized intervention study. RESULTS: The change in the mean number of Early Treatment of Diabetic Retinopathy Study (ETDRS) letters in the graft group 1 year postoperatively was -15 (range -54 to +26), whilst 2 patients experienced a gain of >10 letters. The median preoperative visual acuity (VA) was 0.75 logMAR (range 0.46-2.8), and the mean postoperative VA was 1.48 logMAR (range 0.14-2.8). The change in the mean number of ETDRS letters in the anti-VEGF group was -8 (range -26 to +6); no patients experienced a >10 letter gain. The median preoperative VA was 1.36 logMAR (range 0.58-1.6), and the median postoperative VA was 1.42 logMAR (range 0.44-1.66). CONCLUSIONS: The included patient group is far too small to draw conclusions. However, both gain and loss of VA may be experienced by patients undergoing either treatment method; more gain might be possible for patients with a graft in the absence of complications.

Deferred laser photocoagulation of relaxing retinotomies under silicone oil tamponade to reduce recurrent macular detachment in severe proliferative vitreoretinopathy.

PURPOSE: This study sought to investigate whether, in patients with retinal detachment complicated by proliferative vitreoretinopathy, we can re-attach the retina with a posterior relaxing retinotomy and silicone oil tamponade while postponing laser retinopexy for several months. METHODS: In 13 consecutive patients we applied laser coagulation of the retinotomy edge 15 ± 12 weeks after surgery. Silicone oil was removed 9 ± 6 weeks after laser application. RESULTS: After the retinotomy without laser, some degree of central shifting was seen in all patients, followed by obvious curling in 10 patients. The total follow-up was 24 ± 7 months after retinotomy and 13 ± 9 months after oil removal. The retina was attached in 12 patients at the last visit, with the oil still in situ in three patients. Seven patients, however, required additional surgery. Function remained stable with a mean preoperative and postoperative Snellen visual acuity of 0.09. CONCLUSIONS: Not anchoring retinotomy edges with a laser at the time of surgery allows inward curling and central slippage of retinal edges under silicone oil. This appears to compensate for the retinal fibrosis occurring in the weeks following surgery and may result in less macula-off re-detachments under oil, and potentially, in better visual outcome.

A prospective multicenter randomized placebo-controlled trial of dexamethasone as an adjuvant in the treatment of postoperative bacterial endophthalmitis: interim safety analysis of the study drug and analysis of overall treatment results.

PURPOSE: In an ongoing prospective multicenter randomised placebo-controlled trial we study the adjuvant use of intravitreal dexamethasone in the treatment of patients with suspected bacterial endophthalmitis after phacoemulsification. In accordance with the study protocol, a mid-inclusion interim analysis of the safety of the study drug was performed. PATIENTS AND METHODS: Patients with suspected endophthalmitis after phacoemulsification were asked to participate in this study. A diagnostic vitreous biopsy was taken and the patients received intravitreal injections of 400 micrograms dexamethasone or a placebo, plus 0.2 mg vancomycin and 0.05 mg gentamicin. Injections were repeated after 3 or 4 days. The safety analysis included: the number of eyes with an evisceration; no light perception; or a visual acuity of less than 5/200. Treatment outcome was evaluated in terms of: the percentage of patients with a visual acuity of 20/40 or more and 20/100 or more. RESULTS: The interim analysis included 81 patients with at least 1 year follow-up. Sixty-three patients (65 %) were culture-positive. Safety analysis: 7 eyes were eviscerated (3 dexamethasone, 4 placebo); 4 eyes had no light perception (2 dexamethasone, 2 placebo); and 4 eyes had less than 5/200 vision (3 dexamethasone, 1 placebo). Treatment outcome: 70 % of patients had a visual acuity of at least 20/40. CONCLUSION: The safety analysis does not warrant premature discontinuation of the study. So far, the overall outcome of our treatment regimen, consisting of merely a diagnostic biopsy instead of a vitrectomy and an optimized antibiotic dosing, compares favourably to published literature.

Retinal damage extends beyond the border of the detached retina in fovea-on retinal detachment.

PURPOSE: The aim of this study was to investigate the preoperative and postoperative change in retinal sensitivity in relation to the distance to the retinal detachment (RD) in patients with fovea-on RD. METHODS: We prospectively evaluated 13 patients with fovea-on RD and a healthy control eye. Preoperatively, OCT scans of the RD border and the macula were obtained. The RD border was highlighted on the SLO image. Microperimetry was used to assess the retinal sensitivity at the macula, the RD border and the retina around the RD border. At 6 weeks, 3 and 6 months postoperatively, follow-up examinations of OCT and microperimetry were performed in the study eye. Microperimetry was performed once in control eyes. Microperimetry data were overlaid on the SLO image. The shortest distance to the RD border was calculated for each sensitivity measurement. The change in retinal sensitivity was calculated as control-study. The relation between the change in retinal sensitivity and the distance to the RD border was assessed using a locally weighted scatterplot smoothing curve. RESULTS: Preoperatively, the greatest loss in retinal sensitivity was 21 dB at 3° inside the RD which decreased linearly, through the RD border, and reached a plateau of 2 dB at 4°. For 6 weeks and 3 months postoperatively, the greatest retinal sensitivity loss remained at 3° inside the RD but was 4 dB and sensitivity loss decreased linearly to a plateau of 0 dB at 5° outside the RD. At 6 months postoperatively, the greatest sensitivity loss was 2 dB at 3° inside the RD, and decreased linearly to a plateau of 0 dB at 2° outside the RD. CONCLUSIONS: Retinal damage extends beyond the detached retina. Retinal sensitivity loss of the attached retina decreased drastically as the distance to the RD increased. Postoperative recovery occurred for both attached and detached retina.

Prevalence of vitreoschisis-induced vitreous cortex remnants over the peripheral retinal surface in eyes undergoing vitrectomy for primary rhegmatogenous retinal detachment.

PURPOSE: Unremoved vitreoschisis-induced vitreous cortex remnants over the peripheral retinal surface posterior to the vitreous base (pVCR) may increase the risk of surgical failure after primary rhegmatogenous retinal detachment (RRD) repair. The purpose of this study was to validate our previous findings on pVCR prevalence during vitrectomy for RRD and to examine their association with proliferative vitreoretinopathy (PVR) and surgical failure. METHODS: Prospective observational multisurgeon study of 100 eyes of 100 consecutive patients who underwent vitrectomy for RRD by one of four vitreoretinal surgeons. Collected data included detected pVCR and known PVR risk factors. Pooled analysis with our previous retrospective study (251 eyes of 251 patients) was also performed. RESULTS: Initial PVR (≥C) was present and removed in 6/100 (6%) patients, pVCR were detected in 36/100 (36%) patients, pVCR were removed in 30/36 (83%) patients with pVCR, and 4/36 (11%) patients with pVCR were high myopes (≤-6D). Six per cent (6/100) developed a retinal redetachment, of which 3/6 (50%) had initial PVR (≥C). Surgical failure rates in eyes with and without pVCR were 17% (6/36) and 0% (0/64), respectively. In eyes with pVCR and surgical failure, pVCR were not or not completely removed during the first surgery. Overall analysis showed that pVCR were statistically significantly associated with PVR. CONCLUSIONS: This study confirms our previous findings: a pVCR prevalence of around 35% and an association between pVCR, PVR formation and surgical failure in patients undergoing vitrectomy for RRD. More research is needed to determine which patients would benefit most from pVCR removal.

Vitreoschisis-induced vitreous cortex remnants in proliferative vitreoretinopathy: A comprehensive review from basic research to clinical practice.

Proliferative vitreoretinopathy (PVR) significantly impacts the prognosis of rhegmatogenous retinal detachment (RRD), one of the most critical and increasing causes of vision loss in the Western world. Despite advancements in surgical instruments and techniques, the failure rate due to PVR remains substantial, necessitating additional surgeries and often leading to unsatisfactory visual outcomes. This comprehensive review explores the role of vitreoschisis-induced vitreous cortex remnants (VCR) as a critical, previously under-recognised factor contributing to PVR. Vitreoschisis, a phenomenon where the inner lamellae of the posterior vitreous cortex detach while the outermost layers remain attached to the retina, creates VCR that may contain hyalocytes and serve as scaffolds for fibrocellular proliferation. These remnants are difficult to visualise without triamcinolone acetonide (TA) staining, leading to their frequent lack of recognition in clinical practice. Moreover, removing VCR can be challenging and time-consuming, often requiring meticulous surgical techniques to avoid retinal damage and ensure complete elimination. This review consolidates insights from basic research and clinical practice, emphasising the importance of complete vitreous removal and effective VCR detection and removal to mitigate PVR risks. It highlights the histopathological and clinical evidence supporting the hypothesis that VCR, containing hyalocytes, play a pivotal role in preretinal membrane formation. The review also discusses epidemiological data, surgical management strategies and potential future directions, including improved visualisation techniques and the development of new surgical tools and methods. This review aims to improve surgical outcomes and reduce the frequency and burden of RRD-related complications by addressing VCR as a critical factor in PVR.

The p53 codon 72 polymorphism (rs1042522) is associated with proliferative vitreoretinopathy: the Retina 4 Project.

PURPOSE: To compare the distribution of a p53 gene polymorphism among European subjects undergoing primary retinal detachment (RD) surgery in relation to the development of proliferative vitreoretinopathy (PVR). DESIGN: Case-controlled gene association study conducted as a component of the Retina 4 Project (a European multicenter study). PARTICIPANTS AND CONTROLS: Five hundred fifty DNA samples, 134 with PVR secondary to primary RD and 416 with RD without PVR. METHODS: The p53 codon 72 polymorphism (rs1042522) was analyzed using allele-specific primer polymerase chain reaction. Proportions of genotypes and the proline (Pro-P) homozygote groups between subsamples from different countries were analyzed in 2 phases. In the first, subsamples from Spain and Portugal were analyzed. After significant results were found, samples from the United Kingdom (UK) and The Netherlands were analyzed (second phase). Genotypic and allelic frequencies were compared between cases and controls in the global sample. MAIN OUTCOME MEASURES: Single significant associations with PVR. RESULTS: A significant difference (P<0.05, Fisher exact test) was observed regarding the p53 genotype frequencies at codon 72 between the PVR cases and the non-PVR controls in Spain and Portugal (phase I), but not in the UK or The Netherlands (phase II). Analysis of Pro homozygote carriers between cases and controls revealed differences in Spain (29.01-42.18 and 2.29-10.20, respectively), Portugal (10.49-29.50 and 1.35-8.89, respectively), and The Netherlands (16.49-31.70 and 4.51-15.09, respectively), but no differences in the UK (7.68-18.1 and 4.85-13.94, respectively). The odds ratio of Pro carriers from Spain and Portugal together was 8.12 (95% confidence interval [CI], 3.72-17.69; P<0.05), whereas the odds ratio of Pro carriers from the UK and The Netherlands was 2.12 (95% CI, 0.96-4.68; P = 0.07). All control samples were in Hardy-Weinberg equilibrium. Considering the entire sample, significant differences were found in genotype frequencies between cases (RR, 30.59%; RP, 43.28%; PP, 26.11% [R = Arg; P = Pro]) and controls (RR, 39.66%; RP, 52.64%; PP, 7.69%) and in Pro homozygote carriers between controls (Pro homozygote 95% CI, 18.67-33.52) and cases (Pro homozygote 95% CI, 5.1-10.2). CONCLUSIONS: Results indicate that the Pro variant of p53 codon 72 polymorphism is associated with a higher risk of PVR developing after a primary RD. Further studies are necessary to understand the role of this polymorphism in the development of PVR.

Recombinant tissue plasminogen activator, vitrectomy, and gas for recent submacular hemorrhage displacement due to retinal macroaneurysm.

BACKGROUND: The visual prognosis of submacular hemorrhages caused by a retinal arterial macroaneurysm (RAM) is poor if left untreated. The use of recombinant tissue plasminogen activator (rtPA) has frequently been reported to displace submacular hemorrhages from the foveal area in patients with age-related macular degeneration. This study aims to investigate the results of displacement of recent-onset submacular hemorrhages due to RAM. METHODS: Institutional retrospective interventional case series of 12 patients with macular hemorrhage due to RAM, who underwent pars plana vitrectomy (PPV); followed in 11 by submacular injection of rtPA and gas tamponade. The main outcome measures were displacement of the hemorrhage, complication rate, and visual acuity at 1 month after surgery and at the last follow-up visit. RESULTS: One month after surgery, the hemorrhage had been successfully displaced in ten out of 11 patients. In these ten patients, visual acuity (VA) increased by a mean of 1.2 logMAR at 1 month after surgery. At the last follow-up visit, the mean increase was 1.5 logMAR. Complications consisted of a vitreous hemorrhage and hyphema, retinal detachment, a new submacular hemorrhage, and vitreous hemorrhage after argon laser retinal photocoagulation of the RAM. CONCLUSIONS: PPV with submacular rtPA and gas injection may successfully displace a recently developed submacular hemorrhage in patients with RAM, with a marked improvement in VA that is likely to be greater than if left untreated.

Factor Xa and thrombin stimulate proinflammatory and profibrotic mediator production by retinal pigment epithelial cells: a role in vitreoretinal disorders?

BACKGROUND: Vitreoretinal disorders, including proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR) and exudative age-related macular degeneration (AMD), are a major cause of visual impairment worldwide and can lead to blindness when untreated. Loss of blood-retinal barrier (BRB) integrity associated with vitreoretinal fibrin deposition, inflammation, fibrosis and neovascularization contribute to the pathophysiological processes in these disorders. Retinal pigment epithelial (RPE) cells are well recognized to contribute to vitreoretinal inflammation/fibrosis and are likely to encounter contact with coagulation factor upon loss of BRB integrity. METHODS: An extensive study was performed in which we examined the effect of factor Xa and thrombin on the production of a broad panel of cytokines/chemokines and growth factors by RPE cells. For this purpose we used the ARPE-19 cell line as well as primary RPE cells, a glass slide based array that allows simultaneous detection of 120 cytokines/chemokines and growth factors, ELISA and real-time-quantitative PCR. The involved signaling cascade was examined using specific inhibitors for protease activated receptor (PAR)1, PAR2 and nuclear factor kappa-B (NF-κB). RESULTS: Factor Xa and thrombin regulated the production of cytokines and growth factors (including GM-CSF, IL-6, IL-8, MCP-3, PDGF-AA, PDGF-BB, TIMP-1 and TGF-α) that fit well in the pathobiology of vitreoretinal disease. Blocking studies revealed that the effects were mediated via PAR1 induced NF-κB activation. CONCLUSIONS: Our findings suggest that factor Xa and thrombin can drive vitreoretinal inflammation and fibrosis and should be considered as treatment targets in vitreoretinal disorders such as PVR, PDR and AMD.

Literature review of recombinant tissue plasminogen activator used for recent-onset submacular hemorrhage displacement in age-related macular degeneration.

AIMS: To review and discuss the literature on recombinant tissue plasminogen activator (rtPA) for the treatment of a recent-onset submacular hemorrhage in patients with age-related macular degeneration. METHODS: The administration technique of rtPA, the use of additional gas and vascular endothelial growth factor inhibitors (anti-VEGF), and the displacement rate of submacular hemorrhage and complications were noted from published reports, and a case series from the Rotterdam Eye Hospital (REH). RESULTS: 38 studies with a total of 1,185 patients (1,176 eyes), and 28 patients from the REH were analyzed. Several methods for rtPA administration are available, which can be divided into two groups: submacular rtPA administration with vitrectomy; or intravitreal rtPA administration without vitrectomy. In both groups, the administration of gas and/or anti-VEGF agents could be additional. There appears to be no clear difference in complete displacement or complication rate between the more or the less invasive treatment groups. CONCLUSION: Although intravitreal injection of rtPA and gas only was reported to be as effective as subretinal rtPA with vitrectomy and gas, recent studies tend to use vitrectomy. These data underscore the need for a randomized controlled trial to choose the most effective and safe method of rtPA administration.

Six months treatment with ibopamine in patients with hypotony after vitreoretinal surgery for retinal detachment, uveitis or penetrating trauma.

PURPOSE: To evaluate the effectiveness of 6 months treatment with ibopamine eye drops in raising the intraocular pressure in patients with therapy-resistant hypotony after vitreoretinal surgery for proliferative vitreoretinopathy secondary to rhegmatogenous retinal detachment or penetrating trauma. METHODS: A 2% ibopamine eye drop was topically administered 3 times daily during 24 weeks. RESULTS: Seventeen patients were included. Nine patients were able to continue their treatment up to 24 weeks; their mean intraocular pressure increase was 2.11 mmHg (SE, 0.56; 95% confidence interval, 0.96 to 3.23; P < 0.0005) in comparison with baseline values. Eight patients stopped using ibopamine before 24 weeks because of complains of follicular conjunctivitis or irritation without clinically observable conjunctivitis. In these patients a comparable increase in intraocular pressure was observed up to treatment discontinuation. CONCLUSION: This study confirms that the use of topical ibopamine may result in a sustained increase in intraocular pressure of >2 mmHg in the majority of patients, but was only well tolerated in half of them. There may only be a few patients, however, who will clinically benefit from this rise in intraocular pressure. A better formulation or method of administration would be needed.