Associations of retinal neurovascular dysfunction with inner retinal layer thickness in non-proliferative diabetic retinopathy.

PURPOSE: Neurovascular coupling impairment and inner retinal layer thinning are early detectable retinal changes in diabetes, and both worsen during progression of diabetic retinopathy (DR). However, direct interactions between these features have not been investigated so far. Therefore, we aimed to analyze associations between the retinal functional hyperemic response to light stimulation and the thickness of individual neuroretinal layers in eyes with early non-proliferative DR. METHODS: Thirty patients with type 1 diabetes featuring mild (n = 15) or moderate (n = 15) non-proliferative DR and 14 healthy subjects were included in this cross-sectional study. Retinal vessel diameters were measured before and during illumination with flickering light using a dynamic vessel analyzer. Individual layer thickness in the macula was analyzed from spectral domain optical coherence tomography. RESULTS: Flicker light-induced vessel dilation was significantly reduced in patients compared to healthy controls (veins: 3.0% vs. 6.1%, p < 0.001; arteries: 1.3% vs. 5.1%, p = 0.005). Univariately, the response in retinal veins of diabetes patients correlated significantly with ganglion cell layer (GCL) thickness (r = 0.46, p = 0.010), and negatively with hemoglobin A1c (HbA1c) levels (r=-0.41, p = 0.023) and age (r=-0.38, p = 0.037), but not with baseline diameters, glucose levels, or diabetes duration. In a multiple regression model only GCL thickness (p = 0.017, ß = 0.42) and HbA1c (p = 0.045, ß=-0.35) remained significantly associated with the vascular flicker light response. CONCLUSION: The results indicate that thinner GCL and worse glycemic control both contribute to reduced retinal neurovascular coupling in patients with clinical signs of DR. Progression of neurovascular dysfunction in DR might be related to structural degeneration of the neurovascular complex in the inner retina.

Occurrence of Corneal Staining after Cataract Surgery with and without Chitosan-N-Acetylcysteine Eye Drops.

INTRODUCTION: The objective of this study was to evaluate the prevalence of ocular surface damage assessed by corneal staining scores right after cataract surgery and whether it can be prevented using chitosan-N-acetylcysteine (C-NAC) eye drops. METHODS: We included patients scheduled for routine cataract surgery. Each patient was randomly assigned to one of three groups. Patients in group 1 underwent routine cataract surgery with no additional eye drops. In group 2, patients received C-NAC eye drops after cataract surgery, and in group 3, C-NAC was applied both before and after surgery. Both groups continued the treatment once daily for 4 days. Ocular surface alteration was assessed using the National Eye Institute (NEI) score, and the visual analog scale (VAS) was used to evaluate subjective complaints. RESULTS: Thirty-six patients were included in the final analyses. One hour after cataract surgery, a statistically significant increase in corneal fluorescein staining was observed in all groups, which decreased again after 1 week. There was no significant difference between the groups 1 h after cataract surgery, though a tendency toward lower NEI scores was observed during this time point in group 3. DISCUSSION: Cataract surgery induced ocular surface staining and subjective complaints after 1 h. However, the increase in VAS score was small and probably not clinically relevant. The application of perioperative C-NAC eye drops did reduce the rate of corneal staining after cataract surgery in a clinically relevant manner.

Structure-Function Analysis of MP-3 Microperimetry versus Octopus Perimetry in Central Glaucomatous Visual Field Defects.

INTRODUCTION: The aim of this study was to compare the structure-function relationship with microperimetry and Octopus perimetry in primary open-angle glaucoma (POAG) patients with central visual field (VF) defects. METHODS: Forty eyes of 24 patients with POAG were enrolled. Circumpapillary retinal nerve fiber layer (cpRNFL) analysis measured by spectral-domain optical coherence tomography (SD-OCT) of the superotemporal, temporal, and inferotemporal optic-nerve head sectors were related to corresponding microperimetric and Octopus VF clusters using the G2 grid-pattern with dynamic strategy, respectively. The structure-function relationships of both devices were assessed via a segmented regression, as well as linear regression across overall SD-OCT cpRNFL values and outside normative (<1%) SD-OCT cpRNFL values. RESULTS: Linear and segmented regression fits were similar with both devices. Across overall cpRNFL sectorial values, structure-function relations for the superotemporal, temporal, and inferotemporal sectors were R2 = 0.176 (p = <0.001), R2 = 0.008 (p = 0.069), and R2 = 0.294 (p = <0.001) for microperimetry and R2 = 0.189 (p = <0.001), R2 = 0.020 (p = 0.002), and R2 = 0.326 (p = <0.001) for Octopus perimetry. For corresponding values outside normative limits (<1%), the relationships were R2 = 0.113 (p = <0.001), R2 = 0.001 (p = 0.836), and R2 = 0.420 (p = <0.001) for microperimetry and R2 = 0.192 (p = <0.001), R2 = 0.002, (p = 0.336), and R2 = 0.366 (p = <0.001) for Octopus perimetry. DISCUSSION/CONCLUSION: Structure-function analysis was similar for both devices. Fundus-tracking should be further evaluated in a longitudinal setting in patients affected by glaucoma.

Effect of Cataract Extraction on Retinal Sensitivity Measurements.

INTRODUCTION: Central and paracentral retinal function is often compromised in various retinal diseases. In these conditions, microperimetry is an important tool for assessing retinal sensitivity values. As retinal diseases are prevalent among the elderly, cataract often coexists. This study investigates the effect of cataract surgery on retinal sensitivity in patients with cataract without retinal disease. MATERIAL AND METHODS: A total of 30 patients already scheduled for cataract surgery were enrolled and microperimetry and visual acuity evaluation was performed before and after cataract extraction. The patients were allocated to 1 of 3 study groups in accordance with the main cataract subtype: nuclear, cortical, or posterior subcapsular (PSC) cataract. RESULTS: Visual acuity increased significantly after cataract surgery (from 0.34 to 0.00 logMar, p < 0.001, paired t test). Similarly, median retinal sensitivity increased significantly from 23 dB (IQR 21-25 dB) to 27 dB (IQR 25.75-28 dB) (p < 0.001, Wilcoxon test). The increase of retinal sensitivity after cataract surgery was highest in the PSC cataract group. CONCLUSION: This study showed an increase in retinal sensitivity values after cataract removal, especially in the PSC group. Therefore, coexisting cataract should be considered when interpreting microperimetry results.

Effect of Iatrogenic Traction during Macular Peeling Surgery on Postoperative Microperimetry.

INTRODUCTION: Vitrectomy with peeling of epiretinal membrane (ERM) and internal limiting membrane offers the chance for improvement of metamorphopsia and visual acuity. Microscope integrated intraoperative optical coherence tomography (iOCT) enables real-time imaging of retinal alterations during peeling, such as intraoperative transient retinal thickening owing to tractional forces during peeling. The aim of our study was to measure the amounts of transient retinal thickening due to tractional forces during membrane peeling, as documented with iOCT, and to analyze possible effects on postoperative retinal function. METHODS: This prospective, monocenter study included patients scheduled for pars plana vitrectomy with membrane peeling due to an idiopathic ERM. During peeling, an iOCT device (ReScan700, Carl Zeiss Meditec AG) with continuous OCT-assistance during the peeling procedure, and video documentation of the peeling procedure, was used for the assessment of intraoperative transient retinal thickening owing to tractional forces during peeling. Directly before and 3 months after surgery, macular-OCT scans and microperimetry were performed. RESULTS: Twenty-five eyes of 25 patients were included in the study. Microperimetry could be performed in all patients, while iOCT documentation could be analyzed in 22 patients. Transient retinal thickening owing to tractional forces during peeling could be observed in 14 patients (64%), with a median thickening to 143% of the normal (preoperative) retinal thickness at that location (IQR 132-163). Six patients (24%) developed new deep microscotomata as seen in microperimetry 3 months after surgery, among them were 2 patients who also had transient retinal thickening during peeling. CONCLUSION: New deep microscotomata developed only in a minority of patients with transient retinal thickening owing to tractional forces during peeling.

Reproducibility of Microperimeter 3 (MP-3) Microperimetry in Open-Angle Glaucoma Patients.

PURPOSE: Primary open-angle glaucoma (POAG) is a chronic progressive optic neuropathy, leading to degeneration of retinal ganglion cells and characteristic morphological changes at the optic disc. In advanced stages of the disease, functional tests, such as standard automated perimetry (SAP), are the main diagnostic tools to detect progression. Compared to SAP, microperimetry offers fundus imaging with motion tracking to ensure precise stimulation of certain locations of the retina. Aim of the study was to assess reproducibility of microperimetry compared to SAP in patients with POAG. METHODS: This prospective monocenter study included patients suffering from POAG with visual field defects in the central 20° zone. After inclusion into the study, 3 consecutive study visits were scheduled within 1 month, assessing microperimetry and SAP at each visit. RESULTS: From 19 patients recruited, data from 18 patients could be analyzed. No significant difference between study visits could be detected in mean retinal sensitivity in microperimetry and SAP (microperimetry p = 0.401; SAP p = 0.644; Friedman's 2-way analysis of variance). The intraclass-correlation coefficient was 0.981 (95% CI 0.978-0.984) for microperimetry and 0.948 (95% CI 0.941-0.955) for SAP. Absolute agreement between deep scotoma points was found in 81 test locations (79%) in microperimetry and in 35 test locations (20%) in SAP (p = 0.003, chi-square test). CONCLUSIONS: Microperimetry and conventional perimetry showed high reproducibility, with slightly better performance of microperimetry. However, the reduced angle of visual field in microperimetry limits its application to central glaucomatous field damage.

Intraoperative Optical Coherence Tomography-Guided Membrane Peeling for Surgery of Macular Pucker: Advantages and Limitations.

PURPOSE: Epiretinal membranes (ERMs) are a disorder leading to progressive vision loss and metamorphopsia. The gold standard in therapy is vitrectomy with membrane peeling. The aim of this study was to assess whether the use of intraoperative optical coherence tomography (iOCT), which allows tomographic visualization of the membrane during peeling, enables peeling without staining. METHODS: This prospective study included 30 eyes of 30 patients with idiopathic ERMs scheduled for surgery. Pars plana vitrectomy with iOCT was performed in all cases, whereas staining of ERMs was only performed if needed. Internal limiting membrane (ILM) peeling was performed in case of wrinkled retinal surface after peeling of ERMs. RESULTS: In 63% (n = 19) eyes the ERM could be peeled successfully without use of staining. Nevertheless, in 89% (n = 17) of patients having had ERM peeling without dye, staining of the ILM was performed afterwards for peeling the ILM. Best corrected visual acuity improved in 80% (n = 24) and remained unchanged in 7% (n = 2) 3 months after surgery. There were no significant differences in postoperative results between patients with and without staining for ERM peeling. CONCLUSIONS: Use of iOCT helps to complete ERM peeling in a majority of cases without use of a chromovitrectomy dye, but as iOCT fails to visualize the ILM, chromovitrectomy still facilitates macular surgery in a majority of cases.

One-Year Results after Internal Limiting Membrane Flap Transposition for Surgical Repair of Macular Holes with Respect to Microperimetry.

PURPOSE: Internal limiting membrane (ILM) flap transposition in surgical repair of macular holes represents a new technique offering good anatomical success rates with large macular holes. The aim of the study was to examine microperimetric outcomes 1 year after ILM flap transposition for surgical repair of macular holes. METHODS: Patients with idi-opathic macular holes scheduled for 23-G pars plana vitrectomy with ILM peeling, ILM flap transposition, and SF6 tamponade were examined in a prospective case series. Distance corrected visual acuity (DCVA), optical coherence tomography, and microperimetry were measured before and 1 year after surgery. RESULTS: In all eyes, closure of the macular hole could be achieved. While foveal sensitivity improved in 71%, perifoveal sensitivity improved in 86% of the cases. DCVA improved in 83% and was unchanged in 17% of the cases. CONCLUSIONS: Beside visual acuity, foveal and perifoveal macular sensitivity improved, underlining the functional success of surgery after ILM peeling with ILM flap transposition.

MACULAR CHOROIDAL VOLUME CHANGES AFTER INTRAVITREAL BEVACIZUMAB FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the effect of intravitreal bevacizumab on the macular choroidal volume and the subfoveal choroidal thickness in treatment naïve eyes with exudative age-related macular degeneration. METHODS: The macular choroidal volume and the subfoveal choroidal thickness were measured using enhanced depth imaging optical coherence tomography. After a screening examination, each patient received 3 monthly intravitreal injections of 1.25 mg bevacizumab. One month after the third injection was a final assessment. RESULTS: Forty-seven patients with a mean age of 80 ± 6.4 years were included. The macular choroidal volume decreased significantly from median 4.1 mm (interquartile range 3.4-5.9) to median 3.9 mm (interquartile range 3.1-5.6) between the baseline and final examination (difference -0.46 mm, 95% confidence interval: -0.57 to 0.35, P < 0.001). Similarly, subfoveal choroidal thickness had decreased from 157.0 µm (interquartile range 116.0-244.5) at baseline to 139.0 µm (interquartile range 102.5-212.0) at the final examination (P < 0.001). Both parameters macular choroidal volume at baseline and subfoveal choroidal thickness at baseline were not associated with the response to treatment. CONCLUSION: The macular choroidal volume and the subfoveal choroidal thickness decreased significantly after 3 monthly bevacizumab injections for exudative age-related macular degeneration.

Regulation of retinal oxygen metabolism in humans during graded hypoxia.

Animal experiments indicate that the inner retina keeps its oxygen extraction constant despite systemic hypoxia. For the human retina no such data exist. In the present study we hypothesized that systemic hypoxia does not alter inner retinal oxygen extraction. To test this hypothesis we included 30 healthy male and female subjects aged between 18 and 35 years. All subjects were studied at baseline and during breathing 12% O2 in 88% N2 as well as breathing 15% O2 in 85% N2. Oxygen saturation in a retinal artery (SO2art) and an adjacent retinal vein (SO2vein) were measured using spectroscopic fundus reflectometry. Measurements of retinal venous blood velocity using bidirectional laser Doppler velocimetry and retinal venous diameters using a Retinal Vessel Analyzer (RVA) were combined to calculate retinal blood flow. Oxygen and carbon dioxide partial pressure were measured from earlobe arterialized capillary blood. Retinal blood flow was increased by 43.0 ± 23.2% (P < 0.001) and 30.0 ± 20.9% (P < 0.001) during 12% and 15% O2 breathing, respectively. SO2art as well as SO2vein decreased during both 12% O2 breathing (SO2art: -11.2 ± 4.3%, P < 0.001; SO2vein: -3.9 ± 8.5%, P = 0.012) and 15% O2 breathing (SO2art: -7.9 ± 3.6%, P < 0.001; SO2vein: -4.0 ± 7.0%, P = 0.010). The arteriovenous oxygen difference decreased during both breathing periods (12% O2: -28.9 ± 18.7%; 15% O2: -19.1 ± 16.7%, P < 0.001 each). Calculated oxygen extraction did, however, not change during our experiments (12% O2: -2.8 ± 18.9%, P = 0.65; 15% O2: 2.4 ± 15.8%, P = 0.26). Our results indicate that in healthy humans, oxygen extraction of the inner retina remains constant during systemic hypoxia.

Quality assurance via telephone interviews after cataract surgery: An explorative study.

INTRODUCTION: Cataract surgery is a relatively safe procedure with satisfactory postoperative results in most patients. However, in rare cases severe complications can occur shortly after the intervention. Therefore, patients are advised to undergo an ophthalmological examination postoperatively, which should be performed as soon as possible in case of emergencies. However, exactly when these follow-up visits should take place is still discussed. A time- and cost-saving alternative to this could be short-term postoperative telemedical approaches. The aim of this study was to analyze patient complaints as well as satisfaction with and the best timepoint to perform telephone calls after cataract surgery. METHODS: Patients scheduled for cataract surgery received a telephone call on the surgery day or the day after (study group) during which they were asked about complaints or additional examination visits. Patients without telephone calls served as control group. All patients had a follow-up visit one week after the intervention during which a questionnaire was filled out and the study group was asked about their satisfaction with the telephone calls. RESULTS: 181 patients were recruited in this study. Ocular surface problems were the most common postoperative symptom. More than 80% of the patients were very satisfied with the telephone calls, with patients being contacted on the day of surgery being more calmed than those called on the next day. No difference in additional and planned follow-up visits was found between the study and the control group (P > .40). Postoperative patient complaints (Phi 0.372, P < .001) and additional prescribed therapy (Phi 0.480, P < .001) were moderately associated with additional visits. CONCLUSION: Satisfaction with telephone reviews shortly after cataract surgery was very high and contacting patients on the evening of the day of the procedure could be a time- and cost-saving alternative to short-term in-house follow-up visits.

Repeatability of biometry in patients with meibomian gland dysfunction before and after vectored thermal pulsation therapy: A randomized, controlled trial.

PURPOSE: To evaluate the effect of vectored thermal pulsation therapy (VTPT) on the repeatability of biometry readings of two different optical biometers in patients with meibomian gland dysfunction (MGD). METHODS: Patients affected by MGD were included in this prospective, randomized, controlled, investigator-masked study. One eye was randomized to VTPT (LipiFlow®, Johnson & Johnson), and the contralateral eye served as a control. Three visits were scheduled at baseline, 2 weeks and 3 months after the treatment. The main outcome parameter of the study was the repeatability of three calculations of emmetropic intraocular lens power (EIOLP) at the 3 months visit as compared to baseline using an optical biometer (IOLMaster® 700, Carl Zeiss Meditec AG). Repeatability of different keratometry values obtained by the optical biometer and a Placido-disc topographer (MS-39®, CSO) served as secondary outcome parameters. RESULTS: Twenty-nine patients were included in the final analysis. While tear film parameters improved in the study eyes, there were no significant differences regarding the repeatability of three EIOLP measurements between baseline and 3-months-visit in both eyes (p > 0.05) and keratometry measurements in both the optical biometer and the Placido-disc topographer. Remarkably, throughout all study visits, there were some outliers regarding the repeatability of measurements. CONCLUSION: While both devices showed high repeatability regarding EIOLP and keratometry, future studies are needed to detect high-risk patients for poor repeatability.

Rotational stability and capsular bag performance of a hydrophobic acrylic open-loop single-piece intraocular lens.

PURPOSE: To evaluate the rotational stability and capsular bag performance of a blue light-absorbing hydrophobic acrylic open-loop single-piece intraocular lens (IOL) with a blast-finished anchor wing haptic design during the first 6 postoperative months. METHODS: In this prospective clinical study, patients with age-related cataract and potential postoperative corrected distance visual acuity (CDVA) of 0.2 logMAR or better were included. The patients received a non-toric hydrophobic acrylic single-piece IOL with an axis mark (YST0.00; Nidek Co. Ltd, Japan). Surgeries were video-taped. Retroillumination images were acquired 1 h, 1 week and 6 months postoperatively. Rotational stability was assessed by precise image overlay. At 6 months, Purkinje meter measurements were performed to evaluate tilt and decentration. RESULTS: In total, 100 eyes of 77 patients were included in the analysis. Mean absolute rotation was 2.1 ± 1.7° (median 1.7, range: 0-7.9) at 6 months (1 h - 6 months postoperatively). IOL rotation was ≤3° and ≤6° in 74 (74%) and 98 (98%) eyes, respectively. Mean absolute IOL rotation from the end of surgery to 6 months was 2.5 ± 2.2° (median 2.3, range: 0-15.6; n = 78). Mean tilt (pupillary axis) and decentration were 4.1 ± 1.9° (median 4.0, range: 0.5-8.2) and 0.35 ± 0.17 mm (median 0.32, range: 0.06-0.91) respectively (n = 84). Postoperatively, 98 (98%) eyes achieved a CDVA of 0.2 logMAR or better, 95 (95%) of ≤0.1 and 81 (81%) of ≤0.0. CONCLUSIONS: This hydrophobic acrylic single-piece IOL showed an excellent rotational stability and capsular bag position with low tilt and decentration values.

Role of endothelin-A receptors in optic nerve head red cell flux regulation during isometric exercise in healthy humans.

Endothelin-1 (ET-1) is an important regulator of vascular tone in the eye. It appears to play a role in ocular disease because of its strong vasoconstrictor action, its role in intraocular pressure homeostasis, and its neurotoxic potential. We have previously shown that ET-1 is involved in choroidal red cell flux (RCF) regulation during isometric exercise in healthy humans. In the present study we hypothesized that ET-1 also plays a role in optic nerve head (ONH) RCF regulation during isometric exercise. To test this hypothesis, we performed a randomized, double-masked, placebo-controlled, two-way crossover study in 15 healthy volunteers. Subjects were randomized to receive intravenous infusions of the specific endothelin type A receptor antagonist BQ-123 and placebo on two different study days. During these infusion periods, subjects performed squatting for 6 min to increase ocular perfusion pressure (OPP). ONH RCF was assessed with laser-Doppler flowmetry, and OPP was calculated from mean arterial pressure and intraocular pressure. BQ-123 did not change OPP or ONH RCF at baseline. The relative increase in OPP during isometric exercise was comparable between both groups (between 84 and 88%, P = 0.76 between groups; P < 0.001 vs. baseline). Isometric exercise increased ONH RCF during placebo and BQ-123, but the increase was more pronounced when the endothelin type-A receptor antagonist was administered (placebo, 27.3 ± 5.4%; and BQ-123, 39.2 ± 4.4%; P = 0.007 between groups). The present data indicate that ET-1 regulates red cell flux in the ONH beyond the autoregulatory range.

Role of nitric oxide in optic nerve head blood flow regulation during an experimental increase in intraocular pressure in healthy humans.

The present study set out to investigate whether nitric oxide, a potent vasodilator, is involved in the regulatory processes in optic nerve head blood flow during an experimental increase in intraocular pressure (IOP). The study was conducted in a randomized, double-masked, placebo-controlled, three way cross-over design. 12 healthy subjects were scheduled to receive either L-NMMA (an unspecific nitric oxide synthase inhibitor), phenylephrine (an α-adrenoceptor agonist) or placebo on three different study days. Optic nerve head blood flow was measured using laser Doppler flowmetry and IOP was increased stepwise with a suction cup. Mean arterial pressure (MAP) and IOP were measured non-invasively and ocular perfusion pressure (OPP) was calculated as OPP = 2/3 MAP-IOP. Administration of L-NMMA and phenylephrine significantly increased MAP and therefore OPP at rest (p < 0.01). L-NMMA significantly reduced baseline blood flow in the optic nerve head (p < 0.01). Application of the suction cup induced a significant increase in IOP and a decrease in OPP (p < 0.01). During the stepwise increase in IOP, some autoregulatory potential was observed until OPP decreased approximately -30% below baseline. None of the administered substances had an effect on this autoregulatory behavior (p = 0.49). The results of the present study confirm that the human optic nerve head shows some regulatory capacity during a decrease in OPP. Nitric oxide is involved in the regulation of basal vascular tone in the optic nerve head but does not seem to be involved in the regulatory mechanisms during an acute increase in IOP in young healthy subjects.

Effects of orally administered moxaverine on ocular blood flow in healthy subjects.

BACKGROUND: To investigate the effect of orally administered moxaverine (Kollateral forte®) on ocular blood flow in young healthy subjects. METHODS: Sixteen healthy subjects (eight male/eight female) aged between 20 and 32 years were included in this placebo-controlled, double-masked, two-way crossover study. Volunteers received 900 mg moxaverine-hydrochloride administered orally in three equal doses or placebo identical in appearance on 2 study days. Outcome variables were measured at baseline and 5 h after first drug administration. Laser Doppler flowmetry was used to assess choroidal and optic nerve head blood flow. Blood velocities in the retrobulbar vessels were measured with color Doppler imaging. RESULTS: Neither moxaverine nor placebo changed mean arterial pressure or intraocular pressure. Neither moxaverine nor placebo had an effect on choroidal (moxaverine: by 9.5 ± 17.2 %, placebo 3.8 ± 18.8 %, p = 0.54 between groups) or optic nerve head blood flow (moxaverine: 4.8 ± 10.4 %, placebo: 1.8 ± 10.9 %, p = 0.52 between groups). Similarly, administration of moxaverine did not change blood flow velocities or calculated resistance index in the retrobulbar vessels compared to placebo. CONCLUSION: The data of the present study indicate that orally administered moxaverine does not increase ocular blood flow. This is in contrast to previous findings, where parenteral administration of moxaverine lead to a significant increase in choroidal blood flow and blood flow velocities in the retrobulbar vessels. The reason for these differing results is unclear, but may be related to the low bioavailability after oral administration.

Retinal white blood cell flux and systemic blood pressure in patients with type 1 diabetes.

AIMS: There is evidence that altered retinal blood flow and altered retinal blood flow regulation play a role in the development and progression of diabetic retinopathy. We compared the association between systemic blood pressure and retinal white blood cell flux in patients with type 1 diabetes and healthy control subjects. METHODS: The study was performed in 100 patients with type 1 diabetes with no or minimal diabetic retinopathy and a group of 313 age-matched healthy controls. Inclusion criteria were systolic blood pressure ≤ 160 mmHg and diastolic blood pressure ≤ 95 mmHg. None of the subjects took vasoactive medication except insulin. The blue field entoptic technique was used to assess retinal white blood cell flux, velocity and density in the perimacular region. Pressure-flow relationships were calculated for both groups to assess differences in blood flow regulation. RESULTS: Retinal white blood cell flux was comparable between the two study groups. Both type 1 diabetic patients and healthy subjects showed a significant positive correlation between retinal white blood cell flux and mean arterial pressure (diabetic patients: r=0.48; p<0.05, healthy subjects r=0.28). The correlation coefficients between mean arterial pressure and white blood cell flux were significantly higher in patients with diabetes than in the healthy control group (p=0.0459). CONCLUSION: Retinal white blood cell flux, as assessed with the blue-field entoptic technique, is not significantly different between type 1 diabetic patients with no or minimal retinopathy and healthy control subjects. Type 1 diabetic subjects do, however, show an abnormal association between systemic blood pressure and retinal white blood cell flux. This indicates altered autoregulation in early diabetic retinopathy.

Effect of Treatment with Topical Azithromycin or Oral Doxycycline on Tear Film Thickness in Patients with Meibomian Gland Dysfunction: A Randomized Controlled Trial.

Purpose: This prospective, randomized, observer-masked, parallel-group study aimed to compare the effect of topical azithromycin and oral doxycycline on tear film thickness (TFT) and signs and symptoms of ocular surface disease (OSD) in patients with meibomian gland dysfunction (MGD). Methods: Patients were randomized to either receive topical azithromycin or oral doxycycline. After a baseline visit, three follow-up visits at intervals of 2 weeks were scheduled. Main outcome of the study was change in TFT as measured with ultrahigh resolution optical coherence tomography. Results: Twenty patients were included in the analysis. TFT significantly increased in both groups (P = 0.028 vs. baseline) with no difference between the groups (P = 0.096). As secondary outcomes, ocular surface disease index (OSDI) score and composite signs of OSD significantly decreased in both groups (P = 0.023 for OSDI and P = 0.016 for OSD signs vs. baseline). While eye-related adverse events (AEs) occurred more frequently in the azithromycin group, systemic AEs were more common in the doxycycline group. Conclusions: Both treatments improved signs and symptoms of OSD in patients with MGD with no difference between the groups. Due to the higher frequency of systemic side effects of doxycycline, azithromycin eye drops seem to be an alternative with comparable efficacy. Clinical Trial Registration number: NCT03162497.

Bioactivity of enoxaparin in critically ill patients with normal renal function.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Venous thromboembolism is a frequent complication in critically ill patients that has a negative impact on patient outcomes. Critically ill patients have significantly lower plasma anti-factor-Xa activity levels compared with control patients after administration of subcutaneous heparin. The clinical relevance of the different anti-factor-Xa levels after prophylactic doses of low molecular weight heparin (LMWH) in critically ill patients is not completely understood. WHAT THIS STUDY ADDS: The standard dose of 40 mg enoxaparin led to a significant increase in anti-FXa levels in this selected cohort of ICU patients with normal renal function. This study found only subtle pharmacokinetic differences, but a comparable pharmacodynamic action, after enoxaparin administration in critically ill and normal medical ward patients. Thrombin generation with TGA RC-low and TGARC-high reagents was significantly reduced in ICU and normal ward patients after receiving LMWH. Both readouts appear equally useful for estimating the pharmacodynamics of enoxaparin. The ex vivo model of thrombosis was used for the first time in patients to evaluate the anti-thrombotic activity of LMWH. This method did not show any difference in thrombus formation after administration of enoxaparin in the individual group of patients. AIM: In critically ill patients, reduced anti-FXa plasma activity following subcutaneous administration of enoxaparin or nadroparin has been described. In this study, we aimed to investigate the bioactivity of enoxaparin in critically ill patients and controls. METHODS: A prospective, controlled, open label study was performed on a medical intensive care unit (ICU) and a general medical ward. Fifteen ICU patients (male = 12, median age 52 years [IQR 40-65], with a median Simplified Acute Physiology Score of 30 [IQR 18-52]) and sex- and age-matched medical ward patients were included. The anti-FXa plasma activity was measured after a single subcutaneous dose of40 mg enoxaparin. The thrombus size of a clot formed in an ex vivo perfusion chamber and endogenous thrombin potential (ETP) were measured. RESULTS: The anti-FXa plasma activity increased significantly after enoxaparin administration, with peak levels at 3 h after treatment, but was comparable between the ICU and medical ward groups (median 0.16 IU ml-1 [IQR 0-0.22 IU ml-1] vs. 0.2 IU ml-1 [IQR 0.15-0.27 IU ml-1],respectively, P = 0.13). The area under the anti-FXa activity curve from 0­12 h was similar between the groups (median 0.97 IU ml-1 h [IQR0.59-2.1] and 1.48 IU ml-1 h1 [IQR 0.83-1.62], P = 0.42 for the ICU group compared with the control group, respectively). The ETP was lower in the ICU group (P < 0.05) at baseline, but it was comparable at 3 h between the groups. Thrombus size decreased at 3 h compared with pre-dose (P = 0.029) and was not different between the groups. CONCLUSION: Similar bioactivity was achieved with a standard dose of subcutaneous enoxaparin in this selected cohort of ICU and general ward patients with normal renal function.

Retreatment with anti-vascular endothelial growth factor therapy based on changes in visual acuity after initial stabilization of neovascular age-related macular degeneration: 3-year follow-up results.

PURPOSE: To evaluate the 3-year therapeutic benefit of intravitreal bevacizumab in neovascular related macular degeneration (nAMD) in a standard clinical setting involving 3 initial injections and a pro re nata regimen as recommended in the PRONTO study. METHODS: In this interventional clinical study, 181 eyes of 160 consecutive patients with active neovascular related macular degeneration meeting recommended criteria for inclusion and protocol criteria for anti-vascular endothelial growth factor therapy undergoing intravitreal bevacizumab monotherapy were observed. Data of treatment-naive eyes (Group 1, n = 114) were analyzed separately from eyes that had undergone previous photodynamic therapy plus intravitreal triamcinolone (Group 2, n = 67). Re-treatment criteria were based on clinical outcome following the official European label regimen. After 1 year of continuous service at an academic referral center, follow-up was performed in private practices in collaboration with the referral center. Main outcome parameters were best-corrected visual acuity and central retinal thickness. RESULTS: After 3 years, best-corrected visual acuity decreased in the overall population (0.23 ± 0.16 to 0.16 ± 0.21. P = 0.002) and in both groups compared with baseline (0.24 ± 0.21 to 0.17 ± 0.21, Group 1, P = 0.03; 0.22 ± 0.19 to 0.16 ± 0.21, Group 2, P > 0.05), whereas central retinal thickness increased in the overall population (291 ± 92 to 319 ± 110 µm, P = 0.01) and in both groups (291 ± 96 to 325 ± 117 µm, Group 1, P > 0.05; 290 ± 83 to 308 ± 96 µm, Group 2, P > 0.05) because of chronic cystic degeneration changes of the macula. Mean treatment rate was 5.1 ± 3.9 (Group 1) versus 3.7 ± 2.7 (Group 2, P = 0.01). Five cases of severe intraocular inflammation after intravitreal bevacizumab were documented. DISCUSSION: While the functional and morphological benefits persisted for the first year after intravitreal bevacizumab treatment, after this time both functional and morphologic results were disappointing during long-term follow-up with visual acuity loss as the main retreatment criterion. After stabilization of the disease, a monthly follow-up of optical coherence tomography and re-treatment based on morphologic, clinical, and vision outcomes may increase the efficacy in patients with neovascular related macular degeneration under anti-vascular endothelial growth factor treatment.