Three-year clinical outcome of XEN45 Gel Stent implantation versus trabeculectomy in patients with open angle glaucoma.

OBJECTIVE: To reliably compare the three-year clinical outcome and safety of XEN45 Gel Stent implantation (XEN) vs. trabeculectomy (TRAB) in patients with glaucoma. SUBJECT/METHODS: We conducted a retrospective cohort study with patients with primary open angle or pseudoexfoliation glaucoma with uncontrolled intraocular pressure (IOP) undergoing XEN or TRAB at the Innsbruck University Clinic of Ophthalmology and Optometry, Austria and analysed changes in IOP, numbers of IOP-lowering medications, and complete surgical success (i.e., IOP ≤ 18 mmHg, ≥20% IOP reduction and not requiring IOP-lowering medication) up to 36 months postoperatively. RESULTS: Between 2013 and 2019, we performed XEN Gel Stent implantation in 58 eyes and trabeculectomy in 84 eyes. From baseline to 36 months, mean IOP decreased from 23.4 to 13.8 mmHg (mean reduction 35%, 95% confidence interval 23-48%, p < 0.001) in the XEN group and from 25.1 to 11.2 mmHg (mean reduction 50%, 41-60%, p < 0.001) in the TRAB group. TRAB provided higher IOP reduction than XEN Gel Stent implantation at 12, 24, and 36 months (all p < 0.05). In XEN versus TRAB, IOP-lowering medication was required by 98.3% vs. 97.6% before surgery (p = 0.781), differed significantly at month 12 (43.2% vs. 2.0%, p < 0.001)but not at month 24 or 36. Complete surgical success was achieved in 40.0% vs. 62.8% at month 24 (adjusted odds ratio 2.70; 1.04-7.00, p = 0.040) and 27.3% vs. 56.8% at month 36 (4.36; 1.25-15.18, p = 0.021). CONCLUSION: Compared to XEN, TRAB was associated with lower intraocular pressure, less IOP-lowering medication, and higher probability of achieving complete surgical success over a 36-month follow-up period.

CHANGES IN SYSTEMIC LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR AFTER INTRAVITREAL INJECTION OF AFLIBERCEPT OR BROLUCIZUMAB FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To analyze and compare the effects of intravitreal brolucizumab versus aflibercept on systemic vascular endothelial growth factor (VEGF)-A levels in patients with neovascular age-related macular degeneration. METHODS: In this prospective interventional case series study, brolucizumab (6.0 mg/50 µL) or aflibercept (2.0 mg/50 µL) was injected intravitreally in 30 patients each. Blood samples were drawn at baseline and 7 days and 28 days after the first injection. Systemic VEGF-A levels were measured using enzyme-linked immunosorbent assay. Thirty healthy individuals served as controls. RESULTS: The median baseline systemic VEGF-A levels in the brolucizumab, aflibercept, and control groups were 10.8 (8.0-13.2), 12.0 (8.0-18.5), and 10.0 (8.0-15.1) pg/mL, respectively (P = 0.315). In the brolucizumab group, VEGF-A levels significantly decreased to 8.0 (8.0-11.5) pg/mL on Day 7 (P = 0.0254) and to 8.0 (8.0-8.0) pg/mL on Day 28 (P < 0.001). In the aflibercept group, VEGF-A levels significantly decreased to 8.0 (8.0-8.0) pg/mL on Day 7 (P < 0.001) but returned to the baseline level, 12.5 (8.5-14.6) pg/mL, on Day 28 (P = 0.120). Vascular endothelial growth factor-A levels were significantly different between the treatment groups after 28 days (P < 0.001). CONCLUSION: Intravitreal brolucizumab resulted in a sustained reduction of systemic VEGF-A levels until 28 days posttreatment, which raises concerns regarding its safety and long-term effects.

The impact of compliance among patients with diabetic macular oedema treated with intravitreal aflibercept: a 48-month follow-up study.

PURPOSE: This study aimed to compare anatomical and functional outcomes between patients with non-proliferative diabetic retinopathy (NPDR) with diabetic macular oedema (DME) who adhered to intravitreal aflibercept therapy and patients lost to follow-up (LTFU). METHODS: We enrolled 200 patients and recorded the interval between each procedure and the subsequent follow-up visit. Moreover, visual acuity (VA) and anatomical outcomes were measured at each follow-up examination. RESULTS: Among the patients, 103 (51%) patients adhered to intravitreal aflibercept therapy and follow-up examination while 97 (49%) patients were LTFU. Forty-six (47%) patients LTFU who returned for further treatment showed a significant decrease in VA from 0.51 (±0.46) to 0.89 (±0.38) logarithm of the minimum angle of resolution (logMAR) after 48 months (p = 0.004). Compared with the adherent group, the return group showed a worse VA at 48 months (p = 0.036). Further, 1 (1%) patient in the adherent group and 8 (17%) patients in the return group developed a proliferative DR. Patients who were LTFU had a 13.0 times greater chance to develop a proliferative DR (p = 0.022). CONCLUSIONS: Patients who did not adhere to intravitreal aflibercept therapy for DME showed significantly worse visual outcomes compared to patients with good therapy adherence. Moreover, patients with LTFU had a 13 times higher risk of developing a proliferative DR. Considering the potential disease progress, better strategies should be applied to optimize the functional outcome of patients at risk of reduced adherence.

Effects of Intravitreal Aflibercept on the Systemic Insulin-like Growth Factor-I and Vascular Endothelial Growth Factor-A in Patients with Diabetic Retinopathy and Age-Related Macular Degeneration.

PURPOSE: To analyze the effect of intravitreal aflibercept injections on systemic levels of insulin-like growth factor-1 and vascular endothelial growth factor-A in patients with diabetic retinopathy and age-related macular degeneration. METHODS: Vascular endothelial growth factor-A and insulin-like growth factor-1 levels were determined before and one week and four weeks after intravitreal injection of aflibercept (2.0 mg/50 µl) for 19 patients with age-related macular degeneration (mean age, 76 ± 11 years) and 18 patients with diabetic retinopathy (mean age, 64 ± 14 years). Twenty-two healthy individuals were enrolled as controls. RESULTS: A significant decline in systemic vascular endothelial growth factor-A level, from 43 (30-57) pg/ml at baseline to 8 (8-8) pg/ml (p < 0.001) at week one and 17 (8-25) pg/ml (p=0.0054) at week four, was observed in the age-related macular degeneration group. In the diabetic retinopathy group, vascular endothelial growth factor-A levels declined from 53 (35-117) pg/ml to 2 (1-5) pg/ml (p < 0.0001) one week after injection and 16 (13-22) pg/ml four weeks after injection (p=0.0327). At baseline, systemic insulin-like growth factor-1 concentration was higher in the diabetic retinopathy group (57 [37-99] pg/ml) than in the age-related macular degeneration group (35 [24-51] pg/ml) (p=0.0056). A subgroup analysis showed that patients in the proliferative diabetic retinopathy subgroup had significantly higher systemic insulin-like growth factor-1 concentrations (71 [44.7-243] pg/ml) than those in the nonproliferative diabetic retinopathy subgroup (43 [29-66] pg/ml) (p=0.0048). CONCLUSIONS: The difference between the baseline systemic insulin-like growth factor-1 levels of the age-related macular degeneration and diabetic retinopathy groups and the higher insulin-like growth factor-1 levels in the proliferative diabetic retinopathy subgroup one week after aflibercept therapy suggest that insulin-like growth factor-1 may play a role in the pathomechanism of diabetic retinopathy.

Efficiency benchmarks in the surgical management of primary rhegmatogenous retinal detachment: a monocentric register cohort study of operating room time metrics and influential factors.

OBJECTIVES: To investigate the effect of clinical, methodological and logistic factors on operating room (OR) efficiency in the surgical management of primary rhegmatogenous retinal detachment (RRD). DESIGN: Monocentric retrospective register cohort study. SETTING: Single tertiary centre in the western region of Austria. PARTICIPANTS: We audited patients diagnosed with primary RRD who were treated between January 2014 and August 2019. In total, 783 eyes of 776 consecutive patients were included in this study. Various risk factors affecting OR time efficiency and anatomical success after pars plana vitrectomy (PPV) procedures and scleral buckle (SB) surgery were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: OR efficiency was the primary outcome measure. Secondary outcome measures were the primary success rate after PPV procedures and SB surgery. RESULTS: PPV was performed in 641 (81.9%) eyes and SB surgery in 142 (18.1%) eyes. Mean surgical times in PPV and SB under retrobulbar anaesthesia (RA) were 74.0 (±32.6) min and 62.1 (±24.6) min (p<0.001), respectively, while under general anaesthesia (GA), these values were 112.0 (±52.0) min and 76.0 (±22.5) min (p<0.001), respectively. A regression analysis revealed the following main risk factors for prolonged OR time for the surgical management of RRD with PPV (all p<0.001): presence of a giant tear (ß=24.01; 32%), proliferative vitreoretinopathy (PVR)-C (ß=16.43; 22%), surgery postponed for 72 hours after diagnosis (ß=21.40; 29%), GA (ß=23.64; 32%) or surgery performed by a trainee (ß=17.35; 23%). PVR (p=0.022) in PPV cases, after-hours settings (p=0.006) and surgeon experience (p=0.030) in SB cases were independent risk factors for reduced success rates. CONCLUSIONS: OR coordinators should consider various independent clinical (giant tear, PVR-C, advanced detachment), methodological (PPV vs SB) and logistic (GA vs RA, after-hours setting and surgeon experience) factors to improve the success rate and surgical management planning of RRD accurately while optimising OR resources and staff efficiency.

Effects of COVID-19 protective measures on the ophthalmological patient examination with an emphasis on gender-specific differences.

OBJECTIVE: In response to the COVID-19 pandemic, strict hygiene and containment measures have been instituted in the clinical ophthalmological examination to prevent virus transmission. The aim of this study is to assess the effects of these protective measures on the quality of the examination with an emphasis on gender-specific differences. METHODS AND ANALYSIS: An online survey was sent to ophthalmologists in 10 countries. The collected data included demographics, place of work, current professional status, COVID-19 protective measures and their impact on the quality of the examination. Descriptive statistics were used to analyse the data. Fisher's exact test was used to analyse gender differences. RESULTS: A total of 120 responses were collected. 54.0% of the respondents identified as female and 43.4% as male. Over 75% agreed that protective measures made the examination conditions more difficult. The major problems were fogging of the lenses (87.6%) or slit lamp oculars (69.9%), reduced operability of the slit lamp due to protective barriers (60.2%) and time delay due to disinfection measures (68.1%). Significantly more women than men reported that they used filtering face piece (FFP2) instead of surgical masks (p=0.02). More male participants reported that they removed their mask to prevent fogging (p=0.01). 31% of all participants felt that the COVID-19 protective measures reduced the overall quality of slit lamp examination and 43.4% reported a reduced quality of fundoscopic examination. CONCLUSION: COVID-19 related safety measures reduce the feasibility of the clinical ophthalmological examination. Practicable solutions are required to maintain good examination quality without compromising personal safety.

Bilateral cataract surgery improves neurologic brake reaction time and stopping distance in elderly drivers.

AIMS: To determine brake reaction times before and after bilateral cataract surgery in elderly drivers. METHODS: Sixty-four patients were evaluated on the day of and 4 weeks after bilateral cataract surgery. Forty-three healthy individuals with a valid driving licence served as the control group. A driving simulator was used to determine brake reaction times after receiving a visual stimulus. Total brake reaction time (BRT) as well as neurologic reaction time (NRT), foot transfer time (FTT) and brake pedal travel time (BPTT) were measured, and the measurements obtained before and after cataract surgery were compared. The correlations between NRT, best-corrected visual acuity (BCVA) and contrast sensitivity (CS) were assessed. RESULTS: Out of the 64 patients with bilateral cataract, 53 were assessed for postsurgical measurements. All time measures improved significantly after cataract surgery (BRT, 815.7(224) versus 647.9(148) ms; NRT, 364.7(91) versus 283.5(44) ms; FTT, 290.8(62) versus 248.6(58) ms; and BPTT, 160.6(96) versus 116.6(72) ms, p < 0.001). The calculated stopping distance improved significantly after surgery (22.3(6) versus 19.9(4) m at 50 km/h). Best-corrected visual acuity (BCVA) and contrast sensitivity (CS) improved significantly after surgery (0.25(0.2) versus 0.05(0.05), n = 53, p < 0.001; 1.4(0.2) versus 1.6(0.1), p < 0.001, respectively). There was a significant negative correlation between CS and NRT before surgery (r = -0.253, n = 64, p = 0.04, Pearson's correlation). CONCLUSION: Our findings show a significant effect of CS on neurological BRTs and the corresponding stopping distances. This highlights the importance of presurgical CS evaluation as a critical factor in cataract surgery decisions in elderly drivers.

Impact of submacular fluid volume on visual outcome in macula-off rhegmatogenous retinal detachment using automated optical coherence tomography volumetric quantification.

BACKGROUND: We investigated effects of submacular fluid volume (SMFV) on visual outcomes following surgery for macula-off primary rhegmatogenous retinal detachment (RRD) using automated fluid volumetric quantification with optical coherence tomography (OCT). METHODS: We analysed 127 eyes that were surgically treated for macula-off RRDs. We obtained preoperative images following the spectral domain (SD)-OCT dense volume protocol, applied automated retinal segmentation and used an automated algorithm to quantify each eye's SMFV. We used multivariate models to identify various risk factors for impaired visual outcome. RESULTS: Linear regression showed that preoperative SMFV (ß = 0.013; P = .005) was significantly associated with a reduced visual outcome 12 months after the treatment of macula-off RRDs. SMFV was negatively correlated with 12-month postoperative (r = .311; P = .001) visual acuity (VA). The group with low preoperative SMFV (≤9.0 mm3 ) showed an increasing VA up to 12 months postoperatively (P < .001), while the VA did not increase in the group with high SMFV (>9.0 mm3 ) beyond 3 months of follow-up. Patients with a high SMFV were 8.0 times more likely to have worse visual outcomes after 12 months of follow-up (P = .018). CONCLUSIONS: SMFV was negatively correlated with visual outcomes after the surgical treatment of macula-off RRDs. Patients with SMFV <9.0 mm3 12 months after surgery had an 8.0 times greater chance for better visual recovery than patients with high preoperative SMFV. Our findings highlight the efficacy of automated SMFV quantification in predicting surgical outcomes in patients with RRDs, which could be useful in future clinical practice and the development of research models.

Proton beam radiation for iris melanoma: case series and review of literature.

OBJECTIVE: Purpose of this study is to analyse the visual outcomes, the complication and eye retention rate as well as tumour control data of patients treated with proton beam radiation therapy (PBRT) for iris melanoma. METHODS: Retrospective case series and review based on patients' records. All tumours were categorised according to the American Joint Committee of Cancer staging criteria for primary iris melanoma und underwent either sectorial or whole anterior segment PBRT. RESULTS: Thirteen cases were identified of which five received PBRT of the whole anterior segment and eight received sectorial PBRT. Local tumour control after a mean follow-up of 25 months was 92%. Complications after PBRT included cataract (46%), secondary glaucoma (31%), superficial keratitis (15%) and madarosis (8%). Complications were more common in patients necessitating irradiation of the entire anterior segment than in patients which received sectorial irradiation. Eye retention was achieved in all cases. No statistically significant difference in the mean best corrected visual acuity (BCVA) and intraocular pressure (IOP) was found before and after treatment. Comparison of mean BCVA and IOP between different treatment groups (complete anterior segment vs sectorial irradiation) at the last follow-up visit were also not significantly different. No patient developed metastatic disease during follow-up. CONCLUSION: PBRT is a safe and vision preserving therapeutic modality for iris melanoma. Complete irradiation of the anterior segment is associated with higher complication rates.

Systemic counterregulatory response of angiopoietin-2 after aflibercept therapy for nAMD: a potential escape mechanism.

PURPOSE: To analyse the effect of intravitreal aflibercept injections on systemic angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF)-A levels in patients with neovascular age-related macular degeneration (nAMD). METHODS: In a prospective, randomized study, aflibercept (2.0 mg/50 µl) or ranibizumab (0.5 mg/50 µl) was administered intravitreally to 38 treatment-naive patients. Blood samples were taken before, 7 days after, and 28 days after the first intravitreal therapy. Cytokine levels were measured by enzyme-linked immunosorbent assay. Twenty-two age- and sex-matched individuals served as controls. RESULTS: At baseline, there were no significant differences of systemic Ang2 and VEGF-A levels among the treatment and control groups. After intravitreal aflibercept administration, median (interquartile range: IQR) systemic Ang2 was significantly upregulated from 1819 pg/ml (1262-3099) to 2123 pg/ml (1441-3769; p = 0.011) 7 days after the drug injection and remained non-significantly elevated at 1944 pg/ml (1431-2546 pg/ml; p = 0.653) 28 days after the drug injection. Median (IQR) systemic VEGF-A levels were significantly reduced from 43 pg/ml (30-57) to 8 pg/ml (8-8; p < 0.0001) 7 days and 16 pg/ml (8-26; p = 0.001) 28 days after the injection in the aflibercept group. There were no significant effects on systemic VEGF-A and Ang2 levels in the ranibizumab group at any time point following the first injection. CONCLUSION: In this study, we report significant systemic upregulation of Ang2 after intravitreal aflibercept administration. This counterregulatory response may represent a potential escape mechanism from antiangiogenic therapy.

Effect of Timing on Visual Outcomes in Fovea-Involving Retinal Detachments Verified by SD-OCT.

PURPOSE: To investigate the impact of surgical delay after the objectivation of the foveal status by spectral-domain optical coherence tomography (SD-OCT) on visual outcomes in patients with rhegmatogenous retinal detachment (RRD) with foveal involvement. METHODS: A retrospective dataset analysis of 508 eyes of 504 consecutive patients with primary RRD was performed. The primary outcome measure was the best-corrected visual acuity as a function of time between the assessment of the foveal status with SD-OCT upon initial examination at the department and RRD repair. RESULTS: In total, 188 eyes (37.0%) had a complete foveal detachment and 31 (6.1%) eyes had a bisected fovea by the retinal detachment. A hundred eyes with total foveal detachment received surgery within 24 h and 65 eyes between 24 h and 72 h. Visual outcomes for eyes with detached fovea were significantly better when treated within 24 h (0.47 ± 0.39) compared with those treated between 24 h and 72 h (0.84 ± 0.66; p=0.01) after objectivation of the foveal status with SD-OCT. Pars plana vitrectomy was performed in 174 (92.6%) eyes and scleral buckling surgery in 14 (7.4%) eyes with complete foveal involvement of RRD. CONCLUSIONS: Our findings suggest improved visual outcomes for patients receiving surgery within 24 h after a definitive diagnosis of fovea-involving RRD compared to surgical interventions that were further delayed.

Treatment compliance and adherence among patients with diabetic retinopathy and age-related macular degeneration treated by anti-vascular endothelial growth factor under universal health coverage.

PURPOSE: To analyze and compare loss to follow-up (LTFU) rates between patients with diabetic retinopathy (DR) and those with neovascular age-related macular degeneration (nAMD) in patients, receiving treatment with anti-vascular endothelial growth factor (VEGF), under universal health coverage. METHODS: We retrospectively analyzed the relevant data of 1264 patients receiving anti-VEGF therapy, in this cohort study. The observation period ranged from September 01, 2015 to December 31, 2018. Intervals between each procedure and the subsequent follow-up examination were measured. Demographic data, visual acuity (VA), the type of transport for treatment access, and distance between the residence and clinic were evaluated as risk factors for LTFU. RESULTS: We collected data for 841 patients with nAMD (age, 81.0 (± 8.1 years)) and 423 patients with DR (age, 67.7 (± 12.1 years)). The rate of LTFU, for at least 6 months, was 28.8% and 2.9% for patients with DR and nAMD, respectively (p < 0.001). In the DR group, 18.9% patients were lost to follow-up exceeding > 12 months. Multivariate regression analysis showed that advanced age, lack of mobility, and need for assisted transport, poor final VA despite treatment, and decrease in vision during the observational period were independent risk factors for LTFU exceeding 12 months (p < 0.05). CONCLUSIONS: We found a high long-term LTFU rate for patients with DR, despite treatment under universal health coverage. Considering the risk of disease progression, particularly in patients with chronic DR, strategies for better compliance and adherence to therapy should be considered for optimized patient care.

The involvement of NK1 and Y2 receptor in the development of laser-induced CNVs in C57Bl/6N mice.

PURPOSE: to explore whether the NK1 and Y2 receptors are involved in the pathogenesis of laser-induced CNV (choroidal neovascularization) in C57Bl/6N mice. METHODS: CNV was induced by laser damage of Bruch's membrane and the CNV volume was determined by OCT and/or flatmount preparation. First, the development of the CNV volume over time was evaluated. Second, the CNV development in NK1- and Y2 KO mice was analyzed. Third, the effect on the development as well as the regression of CNV by intravitreal injections of the NK1 antagonist SR140333 and the Y2 antagonist BIIEO246 separately and each in combination with Eylea®, was investigated. Furthermore, flatmount CNV volume measurements were correlated to volumes obtained by the in vivo OCT technique. RESULTS: CNV volume peak was observed at day 4 after laser treatment. Compared to wild type mice, NK1 and Y2 KO mice showed significantly smaller CNV volumes. Eylea® and the Y2 antagonist significantly reduced the volume of the developing CNV. In contrast to Eylea® there was no effect of either antagonist on the regression of CNV, additionally no additive effect upon combined Eylea®/antagonist treatment was observed. There was a strong positive correlation between CNV volumes obtained by OCT and flatmount. CONCLUSION: NK1 and Y2 receptors mediate the development of laser-induced CNVs in mice. They seem to play an important role at the developmental stage of CNVs, whereas VEGF via VEGF receptor may be an important mediator throughout the CNV existence. In vivo OCT correlates with flatmount CNV volume, representing a useful tool for in vivo evaluations of CNV over time.

Granin-derived peptides.

The granin family comprises altogether 7 different proteins originating from the diffuse neuroendocrine system and elements of the central and peripheral nervous systems. The family is dominated by three uniquely acidic members, namely chromogranin A (CgA), chromogranin B (CgB) and secretogranin II (SgII). Since the late 1980s it has become evident that these proteins are proteolytically processed, intragranularly and/or extracellularly into a range of biologically active peptides; a number of them with regulatory properties of physiological and/or pathophysiological significance. The aim of this comprehensive overview is to provide an up-to-date insight into the distribution and properties of the well established granin-derived peptides and their putative roles in homeostatic regulations. Hence, focus is directed to peptides derived from the three main granins, e.g. to the chromogranin A derived vasostatins, betagranins, pancreastatin and catestatins, the chromogranin B-derived secretolytin and the secretogranin II-derived secretoneurin (SN). In addition, the distribution and properties of the chromogranin A-derived peptides prochromacin, chromofungin, WE14, parastatin, GE-25 and serpinins, the CgB-peptide PE-11 and the SgII-peptides EM66 and manserin will also be commented on. Finally, the opposing effects of the CgA-derived vasostatin-I and catestatin and the SgII-derived peptide SN on the integrity of the vasculature, myocardial contractility, angiogenesis in wound healing, inflammatory conditions and tumors will be discussed.