Selective retina therapy (SRT) in patients with therapy refractory persistent acute central serous chorioretinopathy (CSC): 3 months functional and morphological results.

PURPOSE: Central serous chorioretinopathy (CSC) is a disease presenting with detachment of the neurosensory retina and characteristic focal leakage on fluorescein angiography. The spontaneous remission rate is 84% within 6 months. In this study, the efficacy of selective retina therapy (SRT) was examined in patients with therapy refractory persistent acute CSC defined by symptoms for at least 6 months and persistent subretinal fluid (SRF) despite eplerenone therapy. MATERIAL AND METHODS: This is a prospective, monocentric observational study in 17 eyes (16 patients, mean age 42 years, 2 female). SRT was performed with the approved R:GEN laser (Lutronic, South Korea), a micropulsed 527-nm Nd:YLF laser device, with a train of 30 pulses of 1.7 µs at 100-Hz repetition rate at the point of focal leakage determined by fluorescein angiography (FA) at baseline (BSL). Visits on BSL, week 4 (wk4), and week 12 (wk12) included best corrected visual acuity (BCVA, logMar), central retinal thickness (CRT) on spectral domain optical coherence tomography (SD-OCT), and FA. Statistical analysis was performed by pair-by-pair comparisons of multiple observations in each case with Bonferroni correction for multiple testing. (IBM SPSS Statistics 25®). RESULTS: Mean CRT at BSL was 387.69 ± 110.4 µm. CRT significantly decreased by 106.31 µm in wk4 (95%-KI: 21.42-191.2; p = 0.01), by 133.63 µm in wk12 (95%-KI: 50.22-217.03; p = 0.001) and by 133.81 µm (95%-KI: 48.88-218.75; p = 0.001) compared to BSL. Treatment success defined as complete resolution of SRF occurred at wk4 in 7/17 eyes (35.3%) and at wk12 in 10/17 eyes (58.8%). Re-SRT was performed in 7/17 eyes (41.2%) after an average of 107.14 ± 96.59 days. Treatment success after Re-SRT was observed in 4/6 eyes (66.6%, 12 weeks after Re-SRT). Mean BCVA did not change significantly from BSL to any later timepoint after adjusting for multiple testing. Notably, eyes with treatment success showed better BCVA at all timepoints and gained more letters compared to failures. CONCLUSION: Single or repetitive SRT may be an effective and safe treatment in 2 of 3 patients suffering from acute persistent CSC after 6 months of symptoms or more. We observed complete resolution of SRF in around 60% of eyes 12 weeks after first SRT treatment and also 12 weeks after Re-SRT treatment in eyes with persistent or recurrent SRF. Results on the long-term course after SRT are still pending.

Development of a Patient-Oriented Organizational Management System for Intravitreal Injection Therapy in a Standardized "Treat-and-Extend" Regime at a University Eye Clinic. / Entwicklung eines patientennahen Organisationsmanagements für die intravitreale Injektionstherapie in einem standardisierten "Treat-and-Extend"-Regime an einer Universitäts-Augenklinik.

BACKGROUND: The treatment of macular edema with intravitreal injections has revolutionized the treatment of associated diseases in ophthalmology. However, with a few exceptions, this is a chronic treatment where patients require many injections and usually need to stay in treatment for years. Patient adherence and control of patient flow are critical to treatment success. In this manuscript, we describe the development of a patient-oriented organization management for intravitreal injections in a university hospital. MATERIAL AND METHODS: In 2015, the intravitreal treatment in our clinic was switched to the treat-and-extend regime. At the same time, the optimization of the previous organizational processes in perioperative management was evaluated. For the period 2015 to 2018, we analyzed and gradually optimized the procedures of our intravitreal injection therapy in a survey with a specialized service provider. RESULTS: Through the analysis of the original processes, the patient appointment was optimized, work processes were summarized, spatially reorganized and there was only a slight increase in the number of staff involved compared with the significant increase in the number of injections. Through these measures, the total in-hospital-time of the patients could be drastically reduced and at the same time the number of patients on one operation day could be multiplied. CONCLUSION: In the context of chronic treatment with intravitreal injections, the care of an increased number of patients is a logistical challenge. By optimizing processes, existing resources can be better used to meet the increased demands. An optimized system offers the patient greater adherence and a better visual outcome largely independent of the medication used.

Vitrectomy with and without encircling band for pseudophakic retinal detachment with inferior breaks: VIPER Study Report No. 3.

PURPOSE: To test if an encircling band improves outcomes in vitrectomy for pseudophakic retinal detachment (PRD) with inferior or with multiple (4 or more) breaks. METHODS: Subgroup analysis of a prospective randomized controlled multicenter trial in patients with uncomplicated PRD assigned either to 20 G vitrectomy plus encircling band (group E1), or 20 G vitrectomy without any buckle (group C), or 23/25 G vitrectomy without any buckle (group E2). The primary endpoint was defined as no indication for any retina reattaching procedure during the review period of 6 months. One hundred out of 257 patients were identified with inferior breaks and 63 patients had 4 or more breaks. RESULTS: In patients with retinal breaks between 5:00 and 7:00, treatment was successful in 77.4% (24/31, treatment arm E1) versus 57.1% (16/28, treatment arm C) (p = 0.301, odds ratio (OR) 1.83, 95% confidence interval (CI) 0.48 to 7.17). In patients with multiple breaks, success rates were 68.2% (15/22, E1) versus. 72.4% (21/29, C, p = 0.46, OR 0.52, CI 0.08-3.65). CONCLUSION: Combining an encircling band with vitrectomy in patients with pseudophakic retinal detachment and inferior or multiple breaks does not significantly improve primary anatomical success in comparison to treatment with 20 G or 23/25 G vitrectomy alone.

Diffuse Unilateral Subacute Neuroretinitis Caused by Ancylostoma Hookworm.

Diffuse unilateral subacute neuroretinitis is an ocular infectious disease caused by several distinct nematodes. Definite identification of the involved nematodes is rarely achieved. We report on the molecular-based genetic identification of an Ancylostoma ceylanicum hookworm implicated in a case of diffuse unilateral subacute neuroretinitis in a child.

The short-term effects of aflibercept on the size of choroidal neovascularization lesion in treatment-resistant neovascular age-related macular degeneration as determined by spectral-domain optical coherence tomography.

BACKGROUND AND OBJECTIVES: To evaluate the changes in the size of choroidal neovascularization (CNV) lesion using spectral domain-optical coherence tomography (SD-OCT) in patients with treatment-resistant neovascular age-related macular degeneration (AMD) who were switched from ranibizumab to aflibercept. MATERIALS AND METHODS: In this prospective case-series, 33 eyes of 30 patients with treatment-resistant neovascular AMD were included. Treatment-resistant neovascular AMD was defined as choriodal neovascularization secondary to AMD determined by subretinal fluid and/or intraretinal fluid/cysts after more than 6 months of monthly ranibizumab therapy. Enrolled eyes were received intravitreal aflibercept injections at weeks 0, 4, and 8. Maximum area of CNV lesion in the cross-sectional area in the B-scan was measured using Heidelberg Eye Explorer software. The same cross-sectional sections containing maximum area of CNV lesion were used during the follow-up. CNV subtypes were determined based on fluorescein angiography images prior to ranibizumab therapy. Main outcome measures were changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), and area of CNV lesion. RESULTS: There were five classic (15%), seven minimally classic (21%), and 21 occult subtypes of CNV (64%). Four weeks after the third injection, BCVA improvement and reduction of the retinal thickness in nine standard ETDRS subfields were significant (both P < 0.001). Regarding and regardless of CNV subtypes, mean area of CNV lesion decreased significantly at final visit. Overall, a dry macula was achieved in 21 eyes (64%) and 12 eyes (36%) showed decreased or unchanged edema. CONCLUSIONS: Switching to aflibercept seems to result in reduction of CNV lesion area in short-term follow-up of patients with treatment-resistant neovascular AMD. Lasers Surg. Med. 48:668-677, 2016. © 2016 Wiley Periodicals, Inc.

Cardiovascular Risk Factors in Central Retinal Artery Occlusion: Results of a Prospective and Standardized Medical Examination.

PURPOSE: To analyze the underlying risk factors in patients with nonarteritic central retinal artery occlusion (CRAO) in a well-defined and homogenous group of patients enrolled in the European Assessment Group for Lysis in the Eye (EAGLE) study. DESIGN: Analysis of the cardiovascular risk factors in a prospective, randomized clinical trial. PARTICIPANTS: Seventy-seven EAGLE patients with nonarteritic CRAO. METHODS: Analysis of vascular risk factors and underlying diseases detected by questionnaire and standardized physical examination within 1 month after occlusion. MAIN OUTCOME MEASURES: The standardized physical examination included carotid Doppler ultrasonography, echocardiography, electrocardiography, blood pressure monitoring, pulse rate, urine analysis, body mass index analysis, and laboratory tests. RESULTS: Seventy-seven of 84 patients had complete datasets for analysis. Fifty-two (67%) patients had cardiovascular risk factors in their medical history, and comprehensive phenotyping identified at least 1 new risk factor in 60 patients (78%; 95% confidence interval, 67%-87%). Thirty-one (40%) had carotid artery stenosis of at least 70%. Eleven patients experienced a stroke, 5 of those within 4 weeks after the CRAO occurred. Arterial hypertension was found in 56 (73%) patients and was newly diagnosed in 12 (16%) study participants. Cardiac diseases were also highly prevalent (22% coronary artery disease, 20% atrial fibrillation, and 17% valvular heart disease). CONCLUSIONS: Previously undiagnosed vascular risk factors were found in 78% of all CRAO patients. The most meaningful risk factor was ipsilateral carotid artery stenosis. A comprehensive and prompt diagnostic work-up is mandatory for all CRAO patients.

Predictors of prognosis and treatment outcome in central retinal artery occlusion: local intra-arterial fibrinolysis vs. conservative treatment.

INTRODUCTION: The study analyses patients' risk factors to determine prognostic and predictive factors in patients with acute central retinal artery occlusion (CRAO) treated in the randomized European Assessment Group for Lysis in the Eye (EAGLE) Study with local intra-arterial fibrinolysis (LIF) or conservative standard treatment (CST). These data could improve patient selection for either method. METHODS: Post hoc statistical analysis of effects of risk factors on overall best corrected visual acuity (BCVA [logarithm of the minimum angle of resolution (logMAR)]) at baseline and month 1 (prognostic effect) and on the difference between outcome of CST and LIF (predictive effect) was conducted. RESULTS: Seventy two of 84 EAGLE datasets were included. Prognostic effect: Patients with coronary heart disease (CHD) presented worse BCVA at baseline (0.39 logMAR, p = 0.0097). Patients with time from occlusion to treatment <12 h showed a trend to better vision gain at month 1 (-0.23 logMAR, p = 0.086), similarly smoking (-0.24 logMAR, p = 0.077). Predictive effect: Age (<60 years favours LIF -0.54 logMAR; >70 years favours CST 0.28 logMAR; interaction p = 0.070) and CHD (favours CST 0.44 logMAR; interaction p = 0.073) might be predictors of therapeutic outcome. There were no strong effects in multivariate analysis. CONCLUSION: CHD, time from occlusion to treatment and smoking influence BCVA at baseline and at month 1 (prognostic effect). Patients treated within 12 h are more likely to profit from treatment. In multivariate analysis, there is no clear trend to benefit from LIF even in patients with young age, no CHD and early treatment. Based on this preliminary report on a rather small sample size, we do not recommend LIF in CRAO patients.

[Avoiding mistakes in anti-VEGF intravitreal injection therapy]. / Indikationen zur intravitrealen Injektionstherapie mit Anti-VEGF für Makulaerkrankungen ­ Fehler vermeiden.

Intravitreal injection (IVI) of drugs for treatment of various macular diseases is now one of the most frequently performed surgical procedures worldwide. As mostly chronic diseases are treated, the indications for treatment often mean a continuous treatment over years with a corresponding effort regarding spatial, personnel and financial resources. The diagnosis and indications for treatment are nowadays mainly made by spectral domain optical coherence tomography (SD-OCT). The ability to clinically assess and evaluate a fluorescence angiography is less practiced, although these are still a component of the indications for intravitreal injections. Therefore, it can happen that despite all diligence patients may receive anti-vascular endothelial growth factor (VEGF) treatment, sometimes permanently, based on a misinterpretation of the macular diagnosis or disease activity and these indications, once made, are rarely questioned or retracted. Therefore, the aim of this manuscript is to point out possible and typical misinterpretations in the indications or continuation of IVI treatment with anti-VEGF by means of case studies and to sensitize for differential diagnoses.

Vitreal levels of erythropoietin are increased in patients with retinal vein occlusion and correlate with vitreal VEGF and the extent of macular edema.

PURPOSE: This study compares vitreal levels of erythropoietin (EPO) in patients with retinal vein occlusion (RVO) with control subjects. In addition, it investigates different RVO disease parameters (time of vein occlusion, patient age, vitreal vascular endothelial growth factor (VEGF) levels, and extent of central macular edema) for possible correlations with vitreal EPO levels. METHODS: Serum and vitreal EPO were measured from 6 patients with branch retinal vein occlusion, 6 patients with central retinal vein occlusion, and 12 control subjects (10 macular puckers and 2 macular holes). RESULTS: Serum EPO levels (9.8 ± 4.9 mU/mL) did not differ between the RVO and control groups and were significantly lower than vitreal EPO levels in all groups. Vitreal EPO was elevated both in branch RVO (91 ± 59 mU/mL) and central RVO (182 ± 70 mU/mL) compared with controls (35 ± 24 mU/mL). Increased vitreal EPO correlated with higher vitreal VEGF (r = 0.64, P = 0.0008) and more pronounced central macular edema (r = 0.66, P = 0.001). CONCLUSION: The results from this study indicate that EPO is locally expressed in the retina and that it is upregulated together with VEGF in RVO eyes. Because of its role both in neuroprotection and angiogenesis, ocular EPO might represent an interesting target to investigate in patients with RVO, especially in light of the current anti-VEGF treatments.

Comparison of Macular Pigment Optical Density in Glaucoma Patients and Healthy Subjects - A Prospective Diagnostic Study.

PURPOSE: To evaluate the relationship between macular pigment optical density (MPOD) and glaucoma. METHODS: Forty-three patients with an established glaucoma diagnosis (25 females, 18 males, mean age 70 (range 34-84)) and 43 healthy controls (28 females, 15 males, mean age 62 (range 30-87)) were included in this prospective diagnostic case-control study. All subjects underwent detailed eye examination including ophthalmoscopy, best-corrected visual acuity, biomicroscopy, measurement of the axial length of the eye, objective refraction, lens status, central foveal thickness on spectral-domain optical coherence tomography (SD-OCT). In all glaucoma patients, a visual field assessment and a measurement of the retinal nerve fibre layer (RNFL) on SD-OCT were done. MPOD was determined using the macula pigment module of the Spectralis HRA+OCT (Heidelberg Engineering GmbH, Heidelberg, Germany) at 0.51°, 1.02° and 1.99° retinal eccentricity using two-wavelength autofluorescence imaging. RESULTS: In the glaucoma group, the median of the visual field mean defect was 5.1 db (quartiles 3.0 and 13.5) and the mean RNFL-thickness global was 65.9 µm (SD ± 16.1). Median MPOD measured at 0.51°, 1.02° and 1.99° retinal eccentricity in the glaucoma group was 0.42 DU, 0.34 DU and 0.13 DU, in the control group 0.40 DU, 0.35 DU and 0.12 DU respectively. There was no statistically significant difference of median MPOD between glaucomatous and control eyes (p=0.510, 0.735, 0.481). No significant relation between MPOD at 1.02 retinal eccentricity and the presence of glare symptoms was found (p=0.948). However, age seems to correlate with median MPOD measured at 1.02 retinal eccentricity (p=0.017). CONCLUSION: There was no evidence for lower MPOD levels in our glaucoma patients; lower MPOD was not related to the presence of glare symptoms. However there seems to be a positive correlation between age and MPOD at 1.02° retinal eccentricity. To further investigate the relation between glare reported by glaucoma patients and glare disability linked to lower MPOD levels, additional studies are necessary that include both detailed inquiry of the quality of glare and a glare quantification and precise analysis of MPOD levels in glaucoma patients.

[Retinal laser treatment-avoiding mistakes]. / Retinale Lasertherapie ­ Fehler vermeiden.

Even in the era of intravitreal injection therapy (intravitreal operative injection of medication, IVOM) for the treatment of macular and retinal diseases, such as age-related macular degeneration (AMD), proliferative diabetic retinopathy (DR) and diabetic macular edema (DME) as well as proliferative stages and/or macular edema due to retinal vein occlusion (RVO), conventional retinal laser treatment is still of importance. It can be focally performed on an on-label basis for DME and macular edema due to branch RVO (BRVO) and its use as panretinal treatment for proliferative stages in retinal diseases as well as for the treatment of retinal holes is undisputed. The spectrum is extended by the treatment of less common diseases, such as retinal hemangioblastoma, macroaneurysms and subhyaloid macular hemorrhage. There is cause for concern that knowledge about the correct performance of retinal laser application might be shifted into the background due to an increase of IVOM treatment, which could lead to an increase in unnecessary errors. The aim of this manuscript is to increase awareness for the correct indications and execution of retinal laser treatment based on case examples of flawed or insufficient treatment.

Optical coherence tomography angiography analysis of macular flow density in glaucoma.

PURPOSE: Modifications in ocular blood flow may play a significant role in glaucoma development. Optical coherence tomography angiography (OCT-A) is based on the detection and analysis of the reflection behaviour of motion in a static environment and therefore is able to quantify the retinal flow density. We used this new technology to examine the density of the active flow vasculature in the macular area in glaucoma patients compared to healthy patients. METHODS: Thirty patients with primary open-angle glaucoma (mean age: 72.6 ± 7.1 years) and 21 healthy patients (mean age: 70.3 ± 8.6 years) were recruited. Patients received perimetry and OCT measurements of the peripapillary retinal nerve fibre layer thickness (RNFLT) and macular retinal thickness and OCT-A of the macular area in the superficial and deep retinal (DR) plexus. Flow density of the OCT-A scan was calculated by binarisation and quantification of the pixel density. RESULTS: Macular flow density was globally and nasally reduced in glaucoma patients in the superficial (globally: p = 0.0203; nasally: p = 0.0003) and DR plexus (globally: p = 0.0113, nasally: p < 0.0001). There was no significant difference between the superficial retina and the DR concerning the flow density. Flow density showed no significant correlation with perimetry results, RNFLT or retinal segment thickness. CONCLUSION: Patients with glaucoma exhibit a reduced macular flow density measured by OCT-A compared to controls. The independence of the macular flow density of the retinal segment thickness changes could indicate an altered vascular element in patients with glaucoma.

How and why SGLT2 inhibitors should be explored as potential treatment option in diabetic retinopathy: clinical concept and methodology.

Patients suffering from type 2 diabetes are at an increased risk of developing classical microvascular complications such as retinopathy, neuropathy, and nephropathy, which represent a significant health burden. Tight control of blood glucose, blood pressure, and serum cholesterol reduce the risk of microvascular complications but effective pharmacologically targeted treatment options for the treatment and prevention of diabetic microangiopathy are still lacking. Pharmacological inhibition of sodium glucose cotransporter 2 (SGLT2) might have the potential to directly protect against microvascular complications and could represent a potential treatment option. Randomized controlled clinical proof of concept trials are needed to investigate a potential central role of SGLT2 inhibitors in the prevention of diabetic microangiopathy and its classical clinical complications of retinopathy, neuropathy, and nephropathy.

Retinal endovascular lysis in ischemic central retinal vein occlusion: one-year results of a pilot study.

PURPOSE: Retinal endovascular lysis is a new therapeutic option for patients with central retinal vein occlusion (CRVO). In this procedure, a fibrinolytic agent is injected directly into a cannulated retinal vein after pars plana vitrectomy. DESIGN: Prospective interventional case series. PARTICIPANTS: Thirteen strictly defined patients with ischemic CRVO. METHODS: Patients with a decimal visual acuity (VA) of 0.2 or worse were scheduled for surgery within the first 5 months after onset of CRVO. A full ocular examination, determination of VA (Early Treatment Diabetic Retinopathy Study charts), and fluorescein angiography were done preoperatively and 6, 12, 26, and 52 weeks postoperatively. MAIN OUTCOME MEASURE: Visual acuity 1 year after retinal endovascular lysis. Secondary study end points were (1) correlation of VA and successful recombinant tissue plasminogen activator injection into a retinal vein, (2) complication rate, and (3) number of additional surgical procedures within the first year after retinal endovascular lysis. RESULTS: All patients had an ischemic CRVO and completed the 1-year follow-up visit. Preoperative decimal VA was 0.063 +0.025/-0.018 (VA range, light perception [LP]-0.2); 6-week postoperative VA, 0.049 +0.024/-0.016 (LP-0.4); 3-month postoperative VA, 0.043 +0.019/-0.014 (LP-0.3); 6-month postoperative VA, 0.035 +0.022/-0.013 (blindness-0.4); and 12-month postoperative VA, 0.04 +0.026/-0.016 (blindness-0.4). Visual acuity changed 1 year after retinal endovascular lysis by -1.923+/-1.619 lines (+6 to -16 lines; P = 0.258). We considered the retinal endovascular lysis procedure to have been technically successful in 10 eyes. Visual changes did not depend on successful lysis. Six eyes developed neovascular glaucoma, of which 2 globes ended up with painful phthisis and had to be removed. Retinal detachment was found in 3 eyes and cataract in 4. Together, the 13 eyes needed 22 additional surgical procedures. Preoperative and postoperative angiographic examinations showed no significant changes. CONCLUSION: Ischemic CRVO patients did not profit from retinal endovascular lysis in this pilot study. Visual results and the risk of developing iris neovascularization and neovascular glaucoma took the natural course. Although these results may be due to the overall bad prognosis of these particular ischemic eyes, the number of postoperative complications is unacceptably high.

Intraoperative optical coherence tomography and ab interno trabecular meshwork surgery with the Trabectome.

IMPORTANCE: This study is the first description of the use of the intraoperative optical coherence tomography (iOCT) for trabecular meshwork surgery with the Trabectome in a regular clinical setting. BACKGROUND: The aim of this study is to evaluate intraoperatively the immediate success of ab interno trabeculotomy with the Trabectome defined as a removal of the trabecular meshwork. DESIGN: This is a retrospective clinical study performed in the University Eye Hospital, Medical School Hannover. PARTICIPANTS: A total of nine consecutive Caucasian patients suffering from primary open angle glaucoma, pigment dispersion glaucoma, or pseudoexfoliation glaucoma took part in the study. METHODS: All patients underwent ab interno trabeculotomy surgery with the Trabectome using a commercially available iOCT to visualize the anterior chamber angle (ACA) before and after the procedure. The visualization was done using a modified Swan-Jacobs lens (all nine patients) or without lens (view from above, five patients). MAIN OUTCOME MEASURES: The main outcome of this study is the success of visualization of the ACA on iOCT, especially the postprocedural visualization of the wound gap after removal of the trabecular meshwork. RESULTS: Using the view from above, the ACA could be visualized before and after the procedure in only two of the five cases. Using the modified Swan-Jacobs lens, the ACA could be visualized before the procedure and the trabecular meshwork opening after the procedure in all nine patients. CONCLUSION: The iOCT can be used to objectify the immediate success of the surgical procedure, ie, the removal of the trabecular meshwork, of ab interno trabeculotomy with the Trabectome. The procedure itself cannot be captured sufficiently via iOCT.

Switch of Intravitreal Therapy for Macular Edema Secondary to Retinal Vein Occlusion from Anti-VEGF to Dexamethasone Implant and Vice Versa.

PURPOSE: To evaluate the anatomical and functional outcome of intravitreal dexamethasone implant for macular edema secondary to central (C) or branch (B) retinal vein occlusion (RVO) in patients with persistent macular edema (ME) refractory to intravitreal antivascular endothelial growth factor (VEGF) treatment compared to treatment naïve patients and to dexamethasone-refractory eyes switched to anti-VEGF. METHODS: Retrospective, observational study including 30 eyes previously treated with anti-VEGF (8 CRVO, 22 BRVO, mean age 69 ± 10 yrs), compared to 11 treatment naïve eyes (6 CRVO, 5 BRVO, 73 ± 11 yrs) and compared to dexamethasone nonresponders (2 CRVO, 4 BRVO, 69 ± 12). Outcome parameters were change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) measured by spectral-domain optical coherence tomography. RESULTS: Mean BCVA improvement after switch to dexamethasone implant was 4 letters (p = 0.08), and treatment naïve eyes gained 10 letters (p = 0.66), while we noted no change in eyes after switch to anti-VEGF (p = 0.74). Median CFT decrease was most pronounced in treatment naïve patients (-437 µm, p = 0.002) compared to anti-VEGF refractory eyes (-170 µm, p = 0.003) and dexamethasone-refractory eyes (-157, p = 0.31). CONCLUSIONS: Dexamethasone significantly reduced ME secondary to RVO refractory to anti-VEGF. Functional gain was limited compared to treatment naïve eyes, probably due to worse BCVA and CFT at baseline in treatment naïve eyes.

Visual and anatomic outcomes after conversion to aflibercept in neovascular age-related macular degeneration: 12-month results.

PURPOSE: To investigate 12-month outcomes of conversion to aflibercept in patients with neovascular age-related macular degeneration resistant to ranibizumab. METHODS: Twenty-two eyes of 19 consecutive patients received 3 monthly aflibercept injections followed by a pro re nata protocol. Spectral-domain optical coherence tomography (OCT) images were obtained before each injection. All 49 cross-sectional OCT B-scans obtained in each examination were investigated and the largest choroidal neovascularization (CNV) size was chosen. The same cross-sectional B-scan sections containing the maximum CNV size were used during the follow-up. RESULTS: After 12 months, best-corrected visual acuity increased from 45.68 ± 20.25 to 59.09 ± 17.50 Early Treatment Diabetic Retinopathy Study letters (p<0.001), central subfield thickness decreased from 399.91 ± 148.85 to 304.55 ± 97.89 µm (p = 0.003), area of CNV declined from 0.38 ± 0.24 to 0.28 ± 0.19 mm2 (p = 0.003), and macular volume improved from 9.64 ± 1.75 to 8.45 ± 0.98 mm3 (p<0.001). There was a significant resolution of intraretinal fluid (p = 0.016), but reduction of subretinal fluid was not significant (p = 0.25). CONCLUSIONS: Visual and anatomic improvement were obtained after conversion to aflibercept.

Intravitreal injection of specific receptor tyrosine kinase inhibitor PTK787/ZK222 584 improves ischemia-induced retinopathy in mice.

BACKGROUND: Retinal neovascularisation occurs under the influence of angiogenic factors that are induced by hypoxia, like vascular endothelial growth factor (VEGF), which is one of the major mediators. PTK/ZK inhibits VEGF signal transduction by blocking the tyrosine kinase of all three VEGF receptors. PTK/ZK is currently being evaluated in clinical trials for angioinhibitory therapy in tumour patients. To avoid potential systemic side effects, local application would be desirable for the treatment of ischemic retinopathies in humans. We therefore investigated the effect of intravitreally applied PTK/ZK in a mouse model for ischemia-induced retinopathy. METHODS: C57BL/6J mice were placed in 75% oxygen on postnatal day 7. On day 12, they were treated with an intravitreal injection of PTK/ZK (5 microM or 40 microM) in one eye and buffer solution in the fellow eye. Afterwards, the animals were kept in room air until intracardial perfusion with fluorescein-dextran on day 17. Retinal whole mounts were prepared and ischemic retinopathy was evaluated using a standardised retinopathy score. RESULTS: A single intravitreal injection of 40 microM PTK/ZK reduced angioproliferative changes compared to the control eye of each animal (n=37). The difference in retinopathy scores was highly significant (P=0.002, Wilcoxon signed-rank test). Injection of 5 microM PTK/ZK did not show a significant antiangiogenic effect. CONCLUSIONS: Tyrosine kinase inhibitors are promising substances not only in cancer therapy, but also in the treatment of ischemic retinopathies that are mediated by VEGF. We showed that in a mouse model for ischemia-induced retinopathy a single intravitreal injection of 40 microM PTK/ZK is capable of significantly reducing angioproliferative retinopathy. The local application of PTK/ZK could be a new way to treat ischemic ocular diseases such as diabetic retinopathy in humans.

Correlation Between Hyperreflective Foci and Clinical Outcomes in Neovascular Age-Related Macular Degeneration After Switching to Aflibercept.

PURPOSE: To assess the correlation between hyperreflective foci (HF) and visual and anatomical outcomes in treatment-resistant neovascular age-related macular degeneration (AMD) using spectral-domain optical coherence tomography (SD-OCT). METHODS: This was a prospective interventional case series. Thirty-three eyes of 30 consecutive patients with treatment-resistant neovascular AMD were enrolled. Intravitreal aflibercept injections were performed at week 0 (baseline), week 4, and week 8. Spectral-domain OCT images were obtained before each injection and 4 weeks after the third injection. The main focus was on the measurement of choroidal neovascularization (CNV) size in the cross-sectional area in the B-scan through the fovea, and HF number along line segments of 1- and 3-mm length passing through the fovea. RESULTS: Mean number of HF in the radius of 500 µm decreased from 8.36 ± 7.58 to 4.15 ± 3.39 (P = 0.02). Mean number of HF in the radius of 1500 µm was reduced from 21.30 ± 12.47 to 10.45 ± 6.34 (P < 0.001). Mean CNV area decreased from 0.35 ± 0.22 to 0.22 ± 0.16 mm2 (P < 0.001). There was a significant positive correlation between HF reduction in the radius of 500 µm and decrease in central subfield thickness (CST) (r = 0.43, P = 0.01), but no statistically significant correlation was found between HF decline in the radius of 1500 µm and other parameters. CONCLUSIONS: Switching from ranibizumab to aflibercept caused significant decrease in the number of HF 1 month after aflibercept upload, and HF decrease in the radius of 500 µm was correlated positively with the reduction in CST.

Ranibizumab for Branch Retinal Vein Occlusion Associated Macular Edema Study (RABAMES): six-month results of a prospective randomized clinical trial.

PURPOSE: To compare standard-of-care grid laser photocoagulation versus intravitreal ranibizumab (IVR) versus a combination of both in the treatment of chronic (>3 months) macular oedema secondary to branch retinal vein occlusion. METHODS: Prospective, randomized, multicentre clinical trial. Thirty patients with a best-corrected visual acuity (BCVA) between 20/320 and 20/40 were randomized 1:1:1 to receive grid laser or three monthly injections of 0.5 mg IVR or both followed by 3 months of observation. RESULTS: Mean change from baseline BCVA at month 6 was +2 letters [laser; 0.04 logMAR, 95% confidence interval (-0.17; 0.25)], +17 letters [IVR; 0.34 (0.19; 0.5)] and +6 letters [combination; 0.12 (0.01; 0.24)] (IVR versus laser p = 0.02 and IVR versus combination p = 0.02). At month 3, mean improvement in central retinal thickness (CRT) was 90.6 µm (laser) (-18.65; 199.8), 379.5 µm (IVR) (204.2; -554.8), and 248 µm (167.2; -328.8) (combination) (IVR versus laser p = 0.005, laser versus combination p = 0.02). During the observation period, CRT improved in laser [37.6 µm (-66.82; 142.0)], but deteriorated in IVR [-142.4 µm (-247.6; -37.16)] and combination [-171.7 µm (-250.4; -92.96)] (laser versus IVR p = 0.01, laser versus combination p = 0.002) indicating recurrent oedema. Less laser retreatments (at 8 weeks) were required in combination group (2/10) than grid group (7/10). CONCLUSION: Six-month results suggest that ranibizumab may be superior to grid laser in improving visual acuity. Grid combined with IVR neither enhanced functional and morphological improvement of IVR nor did it prevent or prolong recurrence of oedema. In IVR groups, CRT increased slowly after stopping injections, whereas improvement in visual acuity was sustained, indicating that morphological changes occur prior to functional impairment.