Dynamics of structural reversal in Bruch's membrane opening-based morphometrics after glaucoma drainage device surgery.

PURPOSE: Structural reversal of disc cupping is a known phenomenon after trabeculectomy. The aim of this retrospective, longitudinal, cross-sectional analysis was to evaluate the postoperative dynamics of Bruch's membrane opening-based morphometrics of the optic nerve head following glaucoma drainage device surgery. METHODS: Forty-three eyes, treated by glaucoma drainage device surgery, were included in the study. Individual changes in the spectral domain optic coherence tomography (SD-OCT) parameters Bruch's membrane opening minimum rim width (BMO-MRW), Bruch's membrane opening minimum rim area (BMO-MRA) and peripapillary retinal nerve fiber layer (RNFL) thickness as well as mean defect in 30-2 perimetry were analyzed. Changes were correlated to postoperative intraocular pressure levels over time. Available follow-up visits were aggregated and grouped into a short-term follow-up (20 to 180 days after surgery), a midterm follow-up (181 to 360 days after surgery) and a long-term follow-up (more than 360 days after surgery). RESULTS: In short-term follow-up, BMO-MRW and BMO-MRA increased significantly (p <= 0.034). This increase correlated negatively with the intraocular pressure at the time of the follow-up (Pearson's rho = - 0.49; p = 0.039). From 6 months after surgery on, there was no statistically significant change in BMO-MRW and BMO-MRA (p >= 0.207). RNFL thickness and mean defect of 30-2 perimetry showed no significant changes after GDD implantation (p >= 0.189). CONCLUSIONS: Lowering of intraocular pressure by glaucoma drainage device surgery leads to an increase of Bruch's membrane opening based parameters in the first 6 months after surgery. These changes have to be taken into account when evaluating patients' longitudinal follow-up after glaucoma drainage device implantation.

Onset of Retinal Pigment Epithelium Atrophy Subsequent to Anti-VEGF Therapy in Patients with Neovascular Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to evaluate risk factors for the development of retinal pigment epithelium (RPE) atrophy in patients with neovascular age-related macular degeneration (nAMD). PROCEDURES: This post hoc analysis of the prospective RESPONSE study includes 52 therapy-naive nAMD patients without baseline RPE atrophy, who were treated with ≥9 anti-vascular endothelial growth factor (VEGF) injections for ≥3 years. RPE atrophy was assessed via multimodal imaging. Baseline aqueous VEGF and serum complement levels (C3d/C3) were measured. Risk factors for atrophy development were evaluated via logistic regression analysis. RESULTS: Atrophy onset was significantly associated with the duration of nAMD (mean 5.34 years; odds ratio = 1.83, p = 0.012). Anti-VEGF injection number, age, C3d/C3 ratio, baseline intraocular VEGF, or delay to the first treatment had no influence on RPE atrophy. CONCLUSIONS: The duration of treatment-requiring nAMD was identified as primary risk factor for the onset of concomitant RPE atrophy after commencing therapy. Targeting concomitant atrophy in nAMD patients might improve the long-term prognosis of the disease.

Intraoperative changes in corneal structure during excimer laser phototherapeutic keratectomy (PTK) assessed by intraoperative optical coherence tomography.

PURPOSE: Excimer laser phototherapeutic keratectomy (PTK) is a safe treatment for superficial corneal opacities, e.g., in corneal dystrophies or degenerations. Nevertheless, no standardized treatment protocols are available and intraoperative monitoring was not possible, so far. Here we evaluate the potential benefits of the intraoperative assessment by microscope-integrated intraoperative optical coherence tomography (MI-OCT) of corneal optical properties during PTK. METHODS: Retrospective study of eight patients (one male, seven females; age range, 43-80 years, mean = 66.1 years) using an 840-nm microscope-integrated spectral-domain OCT (iOCT; OptoMedical Technologies, Luebeck, Germany adapted to HS Hi-R Neo 900A, Haag Streit Surgical, Wedel, Germany). Images were acquired before and after corneal abrasion and after PTK. For PTK, a SCHWIND Amaris 750S excimer laser (SCHWIND eye-tech-solutions GmbH und KO. KG) was used. Parameters assessed were the central corneal thickness (CCT), changes in central depth-dependent corneal tissue intensity (TI), and corneal surface roughness (SR) in cross-sectional images of the cornea. RESULTS: Intraoperative monitoring using microscope-integrated OCT was possible in all patients at all time points. TI of the anterior corneal stroma decreased significantly (p = 0.037) after PTK (T1 = 15.1 ± 3.6, T2 = 15.0 ± 3.84, T3 = 13.7 ± 3.38), but not after corneal abrasion alone, indicating increased transparency caused by excimer laser PTK. CCT was significantly lower after corneal abrasion (p = 0.017), but not after PTK (T1 = 630.4 ± 70 µm, T2 = 544.1 ± 59.4 µm, T3 = 558.3 ± 52.5 µm. SR significantly decreased (p = 0.043) after PTK (T1 = 614.4 ± 37.5 pixels, T2 = 634.4 ± 35.6 pixels, T3 = 611.0 ± 40.3 pixels). CONCLUSIONS: Intraoperative OCT allows real-time imaging during PTK and the assessment of corneal optical transparency and its surface roughness. It has to be clarified in larger studies if these parameters correlate with later postoperative visual outcomes.

Long-term alterations of systemic vascular endothelial growth factor levels in patients treated with ranibizumab for age-related macular degeneration.

PURPOSE: To analyze long-term changes of systemic vascular endothelial growth factor (VEGF) levels in patients treated with ranibizumab for neovascular age-related macular degeneration. METHODS: Sixty-one patients with neovascular age-related macular degeneration and 68 age-matched controls were included in the study. Patients were treated with ranibizumab on a pro re nata regimen. Plasma samples were collected before initiation of treatment and after 1 year (30 patients) or 2 years (31 patients) of treatment. Vascular endothelial growth factor was measured by Luminex microbead analysis. RESULTS: At baseline, patients with neovascular age-related macular degeneration and controls did not differ significantly in VEGF levels (P = 0.062). There was a significant decline in systemic VEGF levels of 39.5% after 1 year (34.2 ± 17.2 pg/mL to 20.7 ± 14.0 pg/mL; P = 7.50 × 10(-5)) and of 46.7% after 2 years (40.4 ± 24.1 pg/mL to 21.5 ± 23.3 pg/mL; P = 2.48 × 10(-4)) of treatment. Patients with persistent activity of choroidal neovascularization showed a significantly smaller decrease of plasma VEGF levels than patients with dry intervals despite the higher number of injections (P = 0.048). CONCLUSION: In addition to immediate effects limited to days if not hours, ranibizumab also leads to long-term alterations of systemic VEGF to subnormal levels. Patients with persistent choroidal neovascularization activity showed a less pronounced VEGF decrease. Therefore, VEGF levels might be a useful marker for treatment response.

Polymorphisms in vascular endothelial growth factor receptor 2 are associated with better response rates to ranibizumab treatment in age-related macular degeneration.

PURPOSE: Intravitreal anti-vascular endothelial growth factor (VEGF) injections are currently the standard treatment for neovascular age-related macular degeneration (AMD), but a broad range of response rates has been observed. We evaluated the association of single nucleotide polymorphisms (SNPs) in VEGF genes and their receptors (VEGFR) with the response rate to ranibizumab in 366 patients with neovascular AMD. DESIGN: Case series study. PARTICIPANTS: A total of 366 eyes of 366 patients with neovascular AMD. METHODS: Visual acuity (VA) was determined at baseline, after 3 monthly ranibizumab injections, and after 1 year of treatment. Genotyping of 126 SNPs in the genes encoding VEGF family members VEGFA, VEGFB, VEGFC, VEGFD (FIGF), and placental growth factor (PGF); VEGF receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4); and the gene encoding pigment epithelium-derived factor (PEDF) (SERPINF1) was performed. MAIN OUTCOME MEASURES: The changes in VA after 3 injections and after 1 year of treatment and their association with VEGF and VEGFR genotypes. RESULTS: Univariate analyses of variance (ANOVAs) revealed a significant effect of SNP rs4576072 in the VEGFR2 gene on VA change after 12 months (F[1,235] = 14.05; P = 0.02). A stepwise linear regression analysis returned a model (P = 0.01) with SNPs rs4576072 and rs6828477 in the VEGFR2 gene as independent predictors for VA change after 12 months, with a mean increase in VA of 0.26 on the logarithm of the minimum angle of resolution (logMAR) scale in patients with 3 contributing minor alleles compared with a loss of 0.03 logMAR in patients with no minor allele. CONCLUSIONS: Polymorphisms in the VEGFR2/KDR gene significantly influence visual outcome in patients receiving ranibizumab treatment for neovascular AMD. This study shows that genetic variation partially explains the wide range of response to ranibizumab treatment, which in the future might help clinicians tailoring medical interventions to individual needs.

Upregulation of TGF-ß1 in experimental proliferative vitreoretinopathy is accompanied by epithelial to mesenchymal transition.

BACKGROUND: Proliferative vitreoretinopathy (PVR) is characterized by epithelial to mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells and consecutive formation of fibrous membranes, leading to retinal redetachment. Transforming growth factor beta (TGF-ß) has been suggested to play an important role in this process, but the role of TGF-ß isoforms is unknown. METHODS: In pigmented rabbits (n = 14), PVR was induced by cryopexy and a full-thickness limbus-parallel incision. PVR was evaluated by indirect ophthalmoscopy. Concentrations of TGF-ß isoforms were determined by multiplex bead assay analysis in aqueous humor (AH) and vitreous samples. EMT marker vimentin was analyzed by western blot. Masson's-trichrome, haematoxilin and eosine (H&E), and immunohistochemical analysis for EMT marker alpha SMA were performed on cross-sections of eyes. RESULTS: PVR was induced in all treated eyes. The number of quadrants affected by PVR was 1 (n = 5), 2 (n = 2), 3 (n = 2), 4 (n = 5). Vimentin and alpha SMA were expressed during PVR development. During PVR development, both TGF-ß1 levels (AH: p = 0.001; vitreous: p = 0.002) and TGF-ß2 levels increased (AH: p = 0.027; vitreous: p = 0.02), while TGF-ß3 was not detected at any timepoint. The increase was more pronounced for TGF-ß1 than for TGF- ß2 (AH: p = 0.002; vitreous: p = 0.0005), and only TGF-ß1 correlated with the amount of PVR (p = 0.024, r = 0,723). CONCLUSIONS: Development of PVR membranes was accompanied by a pronounced upregulation of TGF-ß1, rather than TGF-ß2. Therefore TGF-ß1 could be a promising target for inhibition of PVR.

Evaluation of Bispecific T-Cell Engagers Targeting Murine Cytomegalovirus.

Human cytomegalovirus is a ubiquitous herpesvirus that, while latent in most individuals, poses a great risk to immunocompromised patients. In contrast to directly acting traditional antiviral drugs, such as ganciclovir, we aim to emulate a physiological infection control using T cells. For this, we constructed several bispecific T-cell engager (BiTE) constructs targeting different viral glycoproteins of the murine cytomegalovirus and evaluated them in vitro for their efficacy. To isolate the target specific effect without viral immune evasion, we established stable reporter cell lines expressing the viral target glycoprotein B, and the glycoprotein complexes gN-gM and gH-gL, as well as nano-luciferase (nLuc). First, we evaluated binding capacities using flow cytometry and established killing assays, measuring nLuc-release upon cell lysis. All BiTE constructs proved to be functional mediators for T-cell recruitment and will allow a proof of concept for this treatment option. This might pave the way for strikingly safer immunosuppression in vulnerable patient groups.

Long-term effects of ranibizumab treatment delay in neovascular age-related macular degeneration.

BACKGROUND: Intravitreal injections of ranibizumab are the standard of care for neovascular age-related macular degeneration (AMD). In clinical trials, comparable efficacy has been shown for either monthly injections or as needed injections upon monthly controls. Unlike in trial settings, treatment in clinical routine is often delayed by complex approval procedures of health insurance and limited short-term surgical capacities. METHODS: Eighty-nine patients with neovascular AMD were followed for 12 months. Early treatment diabetic retinopathy study (ETDRS) visual acuity (VA), Radner reading VA and spectral domain optical coherence tomography were performed monthly, with additional fluorescein angiography if needed. After an initial loading phase of three consecutive monthly intravitreal injections with ranibizumab, re-injections were performed when recurrent activity of choroidal neovascularization (CNV) was detected. RESULTS: After an initial increase to a value of +5.0 ± 11.87 ETDRS letters from baseline, VA constantly decreased over 12 months to a value of -0.66 ± 16.82 ETDRS letters below baseline. Central retinal thickness (CRT) decreased from a value of 438.1 ± 191.4 µm at baseline to a value of 289.9 ± 138.6 µm after initial therapy and stabilized at a value of 322.4 ± 199.5 µm. Loss of VA during latency between indication to treat and treatment was significantly greater than re-gain of VA after re-initiation of therapy (-2.2 ± 5.0 versus 0.4 ± 7.4 letters; p = 0.046). CONCLUSIONS: Latency between indication to treat and treatment is responsible for irreversible VA deterioration. A successful PRN treatment regimen for neovascular AMD requires immediate access to therapy after indication.

Adherence to ranibizumab treatment for neovascular age-related macular degeneration in real life.

BACKGROUND: To identify factors and problems influencing treatment adherence in patients undergoing anti-VEGF therapy for neovascular age-related macular degeneration (AMD) under real-life conditions. METHODS: Cross-sectional study was conducted of 95 patients receiving ranibizumab therapy on a pro re nata (PRN) regimen with monthly controls in a tertiary health care clinic. Monthly controls included best corrected visual acuity, slit-lamp examination and spectral-domain optical coherence tomography. Adherence was measured using Kaplan-Meier time-to-discontinuation analysis. Patients were asked to respond to a 16-item questionnaire covering items such as anxiety, subjective benefit, and financial issues of therapy. RESULTS: Forty-two men and 53 women were included. After a mean follow-up time of 675 days (range 63-1008), adherence was 81.1% (77/95). The mean number of follow-up visits was 19 (3-30), the mean number of intravitreal injections was ten (3-23). Seven patients withdrew from treatment due to subjective dissatisfaction with benefit. Other reasons for loss to follow-up were death in one case, serious general disease in three patients, and treatment options closer to home in five cases. Two patients cancelled further follow-up after treatment cessation due to terminal fibrosis. 62.1% of patients were afraid of a negative examination result, whereas 19.0% were afraid of intravitreal injections. A major problem was travel to and from the hospital (46.3%), with 61.5% of patients requiring escort. CONCLUSION: Despite necessary monthly visits, patients showed a high adherence to therapy. The major problem was travel to and from the hospital. From the patients' point of view, anxiety of a negative examination result was more pronounced than fear of intraocular injections, which would be an argument for continuous injections rather than for a PRN regimen.

Intraocular growth factors and cytokines in patients with dry and neovascular age-related macular degeneration.

PURPOSE: To analyze intraocular growth factor and cytokine concentrations in eyes with different stages of age-related macular degeneration (AMD) compared with controls. METHODS: The Clinical Age-Related Maculopathy Staging (CARMS) system was used for assignment of patients into the respective categories. Aqueous humor specimens were taken before cataract surgery in 21 controls (CARMS 1) and in 17 early (CARMS 2) and 16 intermediate (CARMS 3) AMD patients. In 18 neovascular (CARMS 5) AMD patients, specimens were taken immediately before anti-vascular endothelial growth factor intravitreal therapy. Luminex multiplex bead assays were conducted for endostatin, angiogenin, vascular endothelial growth factor, platelet-derived growth factor AA, placental growth factor, thrombospondin 2, and fibroblast growth factor a. RESULTS: Vascular endothelial growth factor concentrations were elevated in CARMS 3 (P = 0.037) and tended to be elevated in CARMS 5 (P = 0.093), whereas levels in CARMS 2 (P = 0.425) were similar to CARMS 1. Platelet-derived growth factor levels were diminished in CARMS 2 (P = 0.020), with a trend to lower levels for CARMS 3 (P = 0.099) and CARMS 5 (P = 0.082) compared with CARMS 1. For CARMS 5, antiangiogenic endostatin was elevated (P < 0.002), while antiangiogenic thrombospondin 2 was reduced (P = 0.029). CONCLUSION: Clinical Age-Related Maculopathy Staging 3 dry AMD was associated with higher vascular endothelial growth factor levels than CARMS 5 neovascular AMD. Therefore, intraocular vascular endothelial growth factor concentrations do not seem to reflect choroidal neovascularization activity in neovascular AMD directly. Platelet-derived growth factor was decreased in most forms of AMD. The antiangiogenic endostatin was exclusively elevated in neovascular AMD, while thrombospondin 2 was reduced. Age-related macular degeneration disease seems to be associated with a generally altered cytokine system.

Vascular endothelial growth factor in patients with exudative age-related macular degeneration treated with ranibizumab.

OBJECTIVES: To analyze the temporal correlations of vascular endothelial growth factor (VEGF) suppression, morphologic recurrence of choroidal neovascularization (CNV), and visual acuity loss in eyes with exudative age-related macular degeneration (AMD) treated with ranibizumab. DESIGN: Nonrandomized, prospective, clinical study. PARTICIPANTS: Forty-seven eyes of 47 patients with exudative AMD undergoing intravitreal ranibizumab injections. METHODS: Aqueous humor specimens were taken before each intravitreal ranibizumab injection. Visual acuity testing, spectral domain optical coherence tomography (SD-OCT), and fundoscopy were performed before each injection. Vascular endothelial growth factor A was measured by Luminex multiplex bead analysis (Luminex Inc., Austin, TX). MAIN OUTCOME MEASURES: Intraocular VEGF concentration, recurrence of CNV activity shown by SD-OCT, and vision loss. RESULTS: Ranibizumab resulted in complete VEGF suppression within a mean period of 37.8 days (standard deviation [SD] ± 4.8 days; range, 26-49 days). Recurrences of CNV activity as determined by SD-OCT occurred 93.7 days (SD ± 69.9 days; range, 57-368 days) after the last ranibizumab treatment. The VEGF levels were never suppressed when a recurrence occurred. Functional recurrence (visual acuity) occurred 114.3 days (SD ± 81.4 days; range, 57-398 days) after previous treatment. The VEGF levels did not differ significantly between baseline and recurrence (69.3 pg/ml vs. 74.14 pg/ml; 95% confidence interval, -18.87 to 9.12). CONCLUSIONS: A monthly intravitreal injection of 0.5 mg ranibizumab yields a durable VEGF inhibition. The recurrences of CNV as determined by SD-OCT are always preceded by a loss of intraocular VEGF suppression and usually followed by loss of visual acuity in the further course.

Success rates of retinal detachment surgery: routine versus emergency setting.

BACKGROUND: Surgery for rhegmatogenous retinal detachment (RRD) should usually be performed as soon as possible. However, a risk of operating in an emergency setting has to be considered against the risk of delaying it. METHODS: In a retrospective, interventional, non-comparative clinical case series we reviewed the charts of all patients who underwent surgery for primary noncomplex RRD between February 1999 and July 2009. The primary anatomical success (PAS) of RRD surgery was the primary outcome measure, which was defined as permanent reattachment of the retina after a single surgical procedure. All cases were classified as (I) surgical cases, which were performed as emergency procedures the night of the patient's admission to the hospital (emergency setting), and as (II) those cases, which were operated in a routine setting during daytime (routine setting). Visual acuity was documented 2 and 6 months after surgery RESULTS: 1810 cases of primary noncomplex RRD were analysed. PAS rates were 88.0 % in the routine setting and 87.3 % in the emergency setting (p = 0.67). While expert surgeons' PAS rates did not differ between routine and emergency, non-experts achieved inferior anatomical results, when performing surgery in the emergency setting (81.6 % vs. 88.3 %; p = 0.02). There was no difference between expert (87.7 %) and non-expert surgeons (88.6 %) in the routine setting (p = 0.75). There was no statistically significant difference in visual acuity. CONCLUSIONS: Prompt RRD surgery in an emergency setting did not improve the anatomical outcome and was worse if performed by non-expert surgeons. The possibility to schedule surgery may improve delivery of care without compromising the outcome. Although we did not see a significant functional difference, there was a trend for better visual acuity for experts and routine setting. If one decides that prompt surgery is necessary, it should only be done by an experienced vitreoretinal surgeon.

Subjective perception versus objective outcome after intravitreal ranibizumab for exudative AMD.

BACKGROUND: The efficacy of ranibizumab in preserving visual acuity in exudative age-related macular degeneration (AMD) has been widely demonstrated. However, statistically significant improvements in outcome measures such as best-corrected visual acuity (BCVA) may not necessarily be clinically relevant. Clinical relevance can be assumed when the treatment success is perceivable for the patient. We therefore investigated the relation between subjective perception of the treatment success and the objective outcome after intravitreal ranibizumab treatment. METHODS: In this prospective interventional case series, patients received three monthly ranibizumab injections for exudative AMD. To assess the subjective study outcome (SSO) 4 weeks after the third injection, patients had to grade the overall trend of visual quality in the treated eye since baseline. Objective changes of functional (BCVA measured with ETDRS reading charts; reading visual acuity (RVA) and reading speed measured with Radner reading charts) and morphological parameters (central retinal thickness measured with OCT) were evaluated. Agreement between SSO and objective parameters was assessed with nonparametric statistical tests. RESULTS: Seventy-four eyes of 74 patients were analyzed. Mean BCVA increased from 55 (SD ±13) ETDRS letters by +3.16 letters (SD ±11.99, p = 0.03). Mean RVA (measured as logRAD score) increased by -0.067 (SD ±0.294, p = 0.052). Fifty patients (68%) perceived a subjective improvement, 16 (21%) no change, and eight (11%) a worsening in the study eye (SSO). SSO was independent of whether treating the better- or worse-seeing eye (p = 0.83). SSO was significantly correlated with BCVA, RVA, and reading speed (as assessed using the critical print size (CPS)) changes (p = 0.002, p < 0.001, and p = 0.002), but showed no correlation to central retinal thickness changes (p = 0.783). Patients gaining ≥ +5 ETDRS letters had a significantly better SSO (p = 0.001). The rate of subjective improvement increased distinctly to >80% among patients gaining ≥ +7 letters. CONCLUSIONS: In this study, 2/3 of patients reported a subjective improvement from ranibizumab injections. Patients' perception was significantly correlated with objective changes in BCVA and reading visual acuity. Our data indicate that the mean threshold for perceived improvement is a +5 to +7 letter gain, which might accordingly be considered clinically meaningful and relevant. Patients' perception was independent of whether the better- or worse-seeing eye was treated.

Delay between medical indication to anti-VEGF treatment in age-related macular degeneration can result in a loss of visual acuity.

BACKGROUND: Complicated approval procedures and limited short-term surgical capacities can result in time delays between the definition of a medical indication for ranibizumab treatment in active neovascular age-related macular degeneration (AMD) and the starting of treatment. This study aimed to evaluate changes in visual acuity and central retinal thickness over time, and their consequences for the patients concerned. METHODS: Sixty-nine patients indicated for first-time ranibizumab treatment and 21 patients with necessary re-treatment were included in the study. Visual acuity and spectral domain optical coherence tomography (SD-OCT) central retinal thickness at the time of the indication examination were compared to values at the first-time treatment and during recurrent ranibizumab treatment. RESULTS: For first-time treatment, the delay between indication and treatment was significantly higher for patients with vision loss compared to those without vision loss (31.6 ± 20.5 vs. 24.0 ± 8.3 days, p = 0.012). The increase in OCT central retinal thickness was 50.4 ± 92.8 µm for patients with vision loss compared to 5.1 ± 63.4 µm for those without vision loss, p = 0.029. A 1.1 logMAR line difference in vision loss was significant at p = 0.01 for patients with a delay in treatment of less than or equal to 28 days (48/69 patients, 69.7%) compared to those with a delay of more than 28 days (21/69 patients, 30.3%). CONCLUSIONS: Even though average visual decay was slow at about one logMAR line over 110 days, individual patients (8.7%) experienced rapid loss of one or more lines within 21 days. Administrative procedures should therefore be expedited so that delays do not exceed 2 weeks for the sake of vision preservation in individual patients.

Electronic compliance monitoring of topical treatment after ophthalmic surgery.

The success of many medical treatments is built on compliance. Electronic monitoring is the most accurate tool to quantify compliance by measuring adherence. In order to assess the efficiency of a recently introduced miniature monitoring device for eye drop application, we evaluated adherence in ophthalmic patients undergoing post-operative short-term topical treatment. This pilot study enrolled 30 outpatients (mean age 61.8 +/- 18.5 years) after cataract (n = 24) and glaucoma filtration surgery (n = 6) applying fixed-combination eye drops containing prednisolone and gentamicin five times daily for 2 weeks. Patients received eye drops in conventional bottles each equipped with a miniature monitoring device recording events of application. Two patients failed to bring back the monitoring device; therefore data collected from only 28 patients could be examined. Data showed highly variable results with a mean dose compliance of 50.2%. Dose compliance was below 25% in approximately one out of five patients. Four cataract patients, but no glaucoma patient, discontinued therapy prematurely. The observed mean dosage interval was calculated for each patient and ranged 4.6-19.7 h. Thirty percent of analysed dosage intervals exceeded 12.0 h. Different patterns of compliance behaviour-like early non-persistence, drug holiday and low treatment frequency could be identified and illustrated using electronic data. Age or gender did not significantly influence compliance rates. Our pilot study demonstrates successful electronic compliance monitoring using a technology capable of continuous data recording over weeks of treatment. The low compliance rate for a relevant part of the patients demonstrates the necessity to study and improve compliance in ophthalmology. In future, new application methods and electronic application devices may improve treatment response in eye care.

[Excision and tectonic covering of a vascular leiomyoma of the ciliary body with large anterior staphyloma using scleral patch graft]. / Exzision und tektonische Deckung eines vaskulären Leiomyoms des Ziliarkörpers mit großem anteriorem Staphylom mittels Sklerapatch.

Benign tumors of the ciliary body are rare and may potentially be confused with uveal melanoma in clinical routine. Clinical findings rarely allow for safe differentiation. Hence primary excisions are frequent. We report the case of a patient with a benign ciliary tumor, which was observed over a total of 13 years and eventually underwent a local tumor resection.

Haloperidol versus haloperidol plus ondansetron for the prophylaxis of postoperative nausea and vomiting after ophthalmologic surgery.

INTRODUCTION: In this prospective, randomized, and double-blinded study we investigated the efficacy of haloperidol (10 microg/kg) and the combination of haloperidol (10 microg/kg) with ondansetron (0.1 mg/kg) for the prophylaxis of postoperative nausea and vomiting (PONV) after ophthalmologic surgery. METHODS: 60 patients (ASA status 1-3) with risk factors for PONV (female, non-smoker, motion sickness or PONV in history, opioids for postoperative analgesia) undergoing retinal or strabismus surgery were included into the study and randomised to the haloperidol group (H-Group) or the haloperidol-ondansetron group (H/O-Group). 20 min before the end of anaesthesia the study medication was given. Nausea, vomiting, pain scores, and adverse events were assessed postoperatively over 24 h. RESULTS: The incidence of PONV was lower for the H/O-Group (23 vs. 57% for the H-Group). Especially the incidence of vomiting was reduced for the H/O-Group (7 vs. 27% in the H-Group). No significant differences could be detected regarding adverse events. CONCLUSION: The single use of haloperidol for the prophylaxis of PONV is doubtful. Better results were obtained with the combination therapy of haloperidol with ondansetron, especially for vomiting.

Evaluation of two-dimensional Bruch's membrane opening minimum rim area for glaucoma diagnostics in a large patient cohort.

PURPOSE: To characterize the two-dimensional parameter Bruch's membrane opening minimum rim area (BMO-MRA) in spectral domain optical coherence tomography (SD-OCT) of the optic nerve head (ONH) compared to minimum rim width (BMO-MRW) and retinal nerve fibre layer (RNFL) thickness in a large patient cohort. METHODS: Case-control, cross-sectional study of 705 eyes of 445 participants. A total of 449 eyes with glaucoma, 67 eyes with ocular hypertension and 189 healthy controls, underwent SD-OCT and confocal laser scanning tomography (CSLT), visual field testing and clinical examination. Morphometric ONH parameters, visual field function and diagnostic power were compared. Main outcome measures were SD-OCT-derived BMO-MRA, BMO-MRW, RNFL thickness and CSLT-derived rim area (DM-RA). RESULTS: Mean ONH area was 2.11 ± 0.57 mm2 ; mean BMO area was 1.89 ± 0.45 mm2 . Correlation of mean deviation in visual field to morphometric parameters was ρ = 0.70, (p < 0.001) for RNFL thickness, ρ = 0.68 (p < 0.001) for BMO-MRA, ρ = 0.66 (p < 0.001) for BMO-MRW. These correlations were not significantly different (p > 0.05), while DM-RA correlated significantly worse (ρ = 0.55; p < 0.001). In receiver operating characteristics, the calculated area under the curve (AUC) and sensitivity at 90% specificity to differentiate glaucoma were 0.87% and 70.1% for BMO-MRA, 0.86% and 68.1% for RNFL thickness, 0.84% and 66.0% for BMO-MRW, 0.82% and 51.3% for DM-RA. CONCLUSIONS: In a heterogenous clinical cohort of glaucoma patients, all analysed SD-OCT parameters excel DM-RA of CSLT. The two-dimensional parameter BMO-MRA shows comparable levels of diagnostic power to detect glaucoma compared to established parameters BMO-MRW and RNFL thickness. Given higher comparability between ONH sizes, BMO-MRA might become an additional standard tool in SD-OCT imaging for glaucoma.