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In this work we evaluated a postprocessing, customized automatic retinal OCT B-scan enhancement software for noise reduction, contrast enhancement and improved depth quality applicable to Heidelberg Engineering Spectralis OCT devices. A trained deep neural network was used to process images from an OCT dataset with ground truth biomarker gradings. Performance was assessed by the evaluation of two expert graders who evaluated image quality for B-scan with a clear preference for enhanced over original images. Objective measures such as SNR and noise estimation showed a significant improvement in quality. Presence grading of seven biomarkers IRF, SRF, ERM, Drusen, RPD, GA and iRORA resulted in similar intergrader agreement. Intergrader agreement was also compared with improvement in IRF and RPD, and disagreement in high variance biomarkers such as GA and iRORA.

Background To investigate anterior scleral thickness in a cohort of healthy subjects using enhanced depth imaging anterior segment optical coherence tomography. Methods Observational case series. The mean scleral thickness in the inferonasal, inferotemporal, superotemporal, and superonasal quadrant was measured 2 mm from the scleral spur on optical coherence tomography in healthy volunteers. Results Fifty-three eyes of 53 Caucasian patients (25 male and 28 female) with an average age of 48.6 years (range: 18 to 92 years) were analysed. The mean scleral thickness was 571 μm (SD 84 μm) in the inferonasal quadrant, 511 μm (SD 80 μm) in the inferotemporal quadrant, 475 (SD 81 μm) in the superotemporal, and 463 (SD 64 μm) in the superonasal quadrant. The mean scleral thickness was significantly different between quadrants (p

This study confirms that fluorescence lifetime imaging ophthalmoscopy is able to identify and quantify macular alterations after surgical reattachment of macula-off rhegmatogenous retinal detachment that relate to visual acuity. Fluorescence lifetime imaging ophthalmoscopy could be a useful noninvasive diagnostic tool to assess eyes after rhegmatogenous retinal detachment repair., Purpose: The purpose of this study was to investigate fluorescence lifetime imaging ophthalmoscopy lifetimes after macula-off rhegmatogenous retinal detachment (RRD) repair. Methods: Fifty-eight patients with successful macula-off RRD reattachment surgery were included. Retinal autofluorescence was excited with 470 nm, and amplitude-weighted mean fluorescence lifetimes (Tm) were measured in a short spectral channel (SSC, 498–560 nm) and a long spectral channel (LSC, 560–720 nm). Tm were obtained within a standardized Early Treatment Diabetic Retinopathy Study grid and correlated with Tm. The unaffected fellow eye served as control. Results: Fifty-eight patients (age: 65 ± 1.6 years, 11 women) were imaged at median 1.5 months postoperatively. Tm were significantly prolongxxxed within areas of previously detached retina in the long spectral channel and particularly in the central subfield in the short spectral channel. Short lifetimes in the center of the Early Treatment Diabetic Retinopathy Study grid correlated with better visual acuity (short spectral channel; r2 = 0.18, P = 0.001, long spectral channel; r2 = 0.08, P = 0.03). Areas of residual subretinal fluid pockets in four RRD eyes displayed short fluorescence lifetimes. Conclusion: Areas of previously detached retina exhibit significant fluorescence lifetime changes. We found a significant correlation of fluorescence lifetimes within the fovea with visual acuity after successful RRD repair. Our data suggests that the prolongation of fluorescence lifetimes in the fovea is mainly driven by loss of macular pigment. Therefore, fluorescence lifetime imaging ophthalmoscopy may be useful in the prediction of long-term functional outcomes after macula-off RRD surgery.

AimTo report long-term outcomes on best-corrected visual acuity (BCVA) and treatment intervals with a treat-and-extend (T&E) regimen in patients with neovascular age-related macular degeneration (nAMD).MethodsThis observational study included treatment-naïve patients with nAMD, treated with aflibercept. A specific T&E protocol without a loading phase and predefined exit criteria was administered. After reaching predefined ‘exit-criteria’, the treatment period was complete, and patients were observed three monthly.ResultsEighty-two patients with a follow-up period of ≥2 years were included. BCVA (mean±SD, ETDRS letters) increased from 51.9±25.2 at baseline to 63.7±17.7 (pConclusionsAfter 4 years of treatment, initial vision gains were maintained with a reasonable treatment burden, even without an initial loading phase. Our results on functional outcomes are comparable with large controlled studies.

We aimed to evaluate the neuroprotective efficacy of rasagiline in pseudophakic patients who had surgery for macula-off rhegmatogenous retinal detachment (RRD). This was a 6-month, prospective, randomized, double-blind, placebo-controlled pilot study. Patients presenting with acute macula-off RRD were recruited and randomized 1:1 to receive rasagiline 1 mg/day or placebo for 7 days. Best-corrected visual acuity (BCVA) and optical coherence tomography were acquired 1 day before as well as 2 days, 3 weeks, 3 months and 6 months after surgery. We screened 26 patients with RRD whereof 23 were eventually included and randomized. The primary outcome was final BCVA. Secondary outcomes included central retinal thickness (CRT) and adverse events (AE). We evaluated photoreceptor cells (prc) recovery through morphological measurements. The baseline characteristics were comparable between groups. BCVA significantly improved in both groups (letters gained: rasagiline 61.5 ± 18.1 vs placebo 55.3 ± 29.2, p = 0.56), but no significant inter-group difference was found at any visit. CRT was stable 3 weeks after surgery onwards, with no inter-group difference. No treatment-emergent AE occurred. Significant prc restoration was observed from 3 weeks to 6 months after surgery, without inter-group difference at either visit. Ellipsoid zone integrity (β = 0.517, p = 0.008) and foveal bulge (β = 0.387, p = 0.038) were significant predictors of good final BCVA. In conclusion, perioperative oral treatment with rasagiline 1 mg/day for 7 days did not show significant benefits on visual or anatomical outcomes in macula-off RRD patients.

The role of microglia in retinal inflammation is still ambiguous. Branch retinal vein occlusion initiates an inflammatory response whereby resident microglia cells are activated. They trigger infiltration of neutrophils that exacerbate blood–retina barrier damage, regulate postischemic inflammation and irreversible loss of neuroretina. Suppression of microglia‐mediated inflammation might bear potential for mitigating functional impairment after retinal vein occlusion (RVO). To test this hypothesis, we depleted microglia by PLX5622 (a selective tyrosine kinase inhibitor that targets the colony‐stimulating factor‐1 receptor) in fractalkine receptor reporter mice (Cx3cr1 gfp/+) subjected to various regimens of PLX5622 treatment and experimental RVO. Effectiveness of microglia suppression and retinal outcomes including retinal thickness as well as ganglion cell survival were compared to a control group of mice with experimental vein occlusion only. PLX5622 caused dramatic suppression of microglia. Despite vein occlusion, reappearance of green fluorescent protein positive cells was strongly impeded with continuous PLX5622 treatment and significantly delayed after its cessation. In depleted mice, retinal proinflammatory cytokine signaling was diminished and retinal ganglion cell survival improved by almost 50% compared to nondepleted animals 3 weeks after vein occlusion. Optical coherence tomography suggested delayed retinal degeneration in depleted mice. In summary, findings indicate that suppression of cells bearing the colony‐stimulating factor‐1 receptor, mainly microglia and monocytes, mitigates ischemic damage and salvages retinal ganglion cells. Blood–retina barrier breakdown seems central in the disease mechanism, and complex interactions between different cell types composing the blood–retina barrier as well as sustained hypoxia might explain why the protective effect was only partial., Main points Microglia have been depleted in ischemic retina by colony‐stimulating factor‐1 receptor inhibition (PLX5622).Three weeks after branch vein occlusion, depleted retinas showed increased retinal ganglion cell survival and delayed inner retina atrophy.

To compare drusen volume between Heidelberg Spectral Domain (SD-) and Zeiss Swept-Source (SS) PlexElite Optical Coherence Tomography (OCT) determined by manual and automated segmentation methods. Thirty-two eyes of 24 patients with Age-Related Macular Degeneration (AMD) and drusen maculopathy were included. In the central 1 and 3 mm ETDRS circle drusen volumes were calculated and compared. Drusen segmentation was performed using automated manufacturer algorithms of the two OCT devices. Then, the automated segmentation was manually corrected and compared and finally analyzed using customized software. Though on SD-OCT, there was a significant difference of mean drusen volume prior to and after manual correction (mean difference: 0.0188 &plusmn, 0.0269 mm3, p &lt, 0.001, corr. p &lt, 0.001, correlation of r = 0.90), there was no difference found on SS-OCT (mean difference: 0.0001 &plusmn, 0.0003 mm3, p = 0.262, corr. p = 0.524, r = 1.0). Heidelberg-acquired mean drusen volume after manual correction was significantly different from Zeiss-acquired drusen volume after manual correction (mean difference: 0.1231 &plusmn, 0.0371 mm3, p &lt, 0.001, r = 0.68). Using customized software, the difference of measurements between both devices decreased and correlation among the measurements improved (mean difference: 0.0547 &plusmn, 0.0744 mm3, p = 0.02, corr. p = 0.08, r = 0.937). Heidelberg SD-OCT, the Zeiss PlexElite SS-OCT, and customized software all measured significantly different drusen volumes. Therefore, devices/algorithms may not be interchangeable. Third-party customized software helps to minimize differences, which may allow a pooling of data of different devices, e.g., in multicenter trials.

In ophthalmology, retinal biological markers, or biomarkers, play a critical role in the management of chronic eye conditions and in the development of new therapeutics. While many imaging technologies used today can visualize these, Optical Coherence Tomography (OCT) is often the tool of choice due to its ability to image retinal structures in three dimensions at micrometer resolution. But with widespread use in clinical routine, and growing prevalence in chronic retinal conditions, the quantity of scans acquired worldwide is surpassing the capacity of retinal specialists to inspect these in meaningful ways. Instead, automated analysis of scans using machine learning algorithms provide a cost effective and reliable alternative to assist ophthalmologists in clinical routine and research. We present a machine learning method capable of consistently identifying a wide range of common retinal biomarkers from OCT scans. Our approach avoids the need for costly segmentation annotations and allows scans to be characterized by biomarker distributions. These can then be used to classify scans based on their underlying pathology in a device-independent way.

IMPORTANCE: Despite the unquestionable effectiveness of anti–vascular endothelial growth factor therapy (VEGF), there is ongoing controversy about potential systemic adverse effects. Besides the direct adverse effects of anti-VEGF agents, other factors associated with the injection itself, such as perioperative blood pressure fluctuations, may contribute to adverse events. OBJECTIVE: To determine blood pressure fluctuations during intravitreal injections. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational study at a tertiary referral center (Department of Ophthalmology, University Hospital Bern, Bern, Switzerland). Consecutive patients scheduled for intravitreal injections were recruited. Data were analyzed between October 2017 and January 2018. MAIN OUTCOMES AND MEASURES: Systolic and diastolic blood pressure, pulse rate, and oxygen saturation were recorded before, during, and after the intravitreal injection. An anxiety questionnaire was completed by all participants. Multivariate regression analysis was used to investigate potential factors associated with blood pressure rise during injections. RESULTS: Two hundred one patients (92 women and 109 men) were included in this study, with a mean age of 68 years (range, 18-93 years). Mean (SD) systolic blood pressure increased from a baseline of 150 (20) mm Hg to 162 (24) mm Hg following the preparation procedure to 168 (24) mm Hg during the injection (P

PURPOSE To evaluate the outcome of an exit strategy in a treat-and-extend regimen for neovascular age-related macular degeneration. METHODS Five hundred and ninety-eight eyes of 488 patients with neovascular age-related macular degeneration receiving intravitreal anti-vascular endothelial growth factor injections according to a treat-and-extend regimen were included in this retrospective study. A treat-and-extend regimen with either interval extension by 2 weeks or shortening by 1 week was used. "Exit criteria" were defined as 3 consecutive injections 16 weeks apart with stable findings after which the patient was exited from treatment and followed up at 3 to 4 monthly intervals without therapy. Best-corrected visual acuity, central retinal thickness at treatment initiation and termination, incidence of recurrence after treatment termination, presence of characteristics in the optical coherence tomography, duration of therapy, number and intervals of injections were analyzed. RESULTS Seventeen percent of all included eyes met the exit criteria. The mean number of anti-vascular endothelial growth factor injections was 23.7 ± 14.7 with a mean treatment duration of 4.5 ± 2.5 years. Twelve percent reached exit with the minimal number of injections. Thirteen percent had recurrent disease after a mean of 37 ± 16 weeks. In the subgroup with recurrent disease, rate of pigment epithelial detachment at treatment termination was significantly higher than without recurrence (77% vs. 30%, P = 0.0018) with a significant higher proportion of serous pigment epithelial detachment (31% vs. 7%, P = 0.0247). CONCLUSION The high percentage of patients meeting the exit criteria and the relatively low incidence of recurrences underline the usefulness of a predefined exit strategy. However, in a subgroup of patients, continuation of therapy may be advisable.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Background Microglia-associated inflammation is closely related to the pathogenesis of various retinal diseases such as uveitis and diabetic retinopathy, which are associated with increased vascular permeability. In this study, we investigated the effect of systemic lipopolysaccharide (LPS) exposure to activation and proliferation of retinal microglia /macrophages. Methods Balb/c and Cx3cr1gfp/+ mice were challenged with LPS (1 mg/kg) daily for four consecutive days. For microglia depletion, mice were treated with colony-stimulating factor 1 receptor (CSF-1R) inhibitor PLX5622 1 week before the first LPS challenge and until the end of the experiment. In vivo imaging of the retina was performed on days 4 and 7 after the first LPS challenge, using optical coherence tomography and fluorescein angiography. Flow cytometry analysis, retinal whole mount, and retinal sections were used to investigate microglia and macrophage infiltration and proliferation after LPS challenge. Cytokines were analyzed in the blood as well as in the retina. Data analysis was performed using unpaired t tests, repeated measures one-way ANOVA, or ordinary one-way ANOVA followed by Tukey’s post hoc analysis. Kruskal-Wallis test followed by Dunn’s multiple comparison tests was used for the analysis of non-normally distributed data. Results Repeated LPS challenge led to activation and proliferation of retinal microglia, infiltration of monocyte-derived macrophages into the retina, and breakdown of the blood-retina barrier (BRB) accompanied by accumulation of sub-retinal fluid. Using in vivo imaging, we show that the breakdown of the BRB is highly reproducible but transitory. Acute but not chronic systemic exposure to LPS triggered a robust release of inflammatory mediators in the retina with minimal effects in the blood plasma. Inhibition of the CSF-1R by PLX5622 resulted in depletion of retinal microglia, suppression of cytokine production in the retina, and prevention of BRB breakdown. Conclusions These findings suggest that microglia/macrophages play an important role in the pathology of retinal disorders characterized by breakdown of the BRB, and suppression of their activation may be a potential therapeutic target for such retinopathies. Electronic supplementary material The online version of this article (10.1186/s12974-018-1373-4) contains supplementary material, which is available to authorized users.

PURPOSE To analyze retinal blood flow before and after cataract surgery using swept-source optical coherence tomography angiography (SS-OCTA). METHODS Prospective observational study. Consecutive patients were recruited and scanned using SS-OCTA before and after cataract surgery. Laser flare photometry were performed post-surgery. Perfusion and vessel density of superficial (SCP) and deep capillary plexuses (DCP) of the 3 × 3 mm images as well as foveal avascular zone (FAZ) measurements were assessed. Vessel continuity, vessel visibility and presence of artefacts were evaluated by two blinded graders using a predefined grading protocol. RESULTS Thirteen eyes of 12 patients met the inclusion criteria. There was a significant increase of perfusion and vessel densities in both the SCP and the DCP after cataract surgery within the 3 × 3 mm images. Significantly better distinguishability of FAZ border was observed postoperatively in both SCP and DCP, however, FAZ area and perimeter measurements did not significantly change after cataract surgery. Mean number of motion artifacts in SCP and DCP numerically decreased by 37% (P = .089) and 42% (P = .080). CONCLUSIONS Lens opacities have a significant influence on retinal blood flow measurements in SS-OCTA and should be considered in quantitative vessel analysis. Inflammation may also impact the assessment of density parameters. FAZ measurements seems to be the most robust parameters in terms of media opacity.

AIMS To investigate the prognostic significance of macular capillary drop-out and previous panretinal laser photocoagulation in diabetic macular oedema treated with intravitreal ranibizumab. METHODS Retrospective observational case series. Treatment-naive patients with diabetic macular oedema that had been treated with intravitreal ranibizumab as per the RESTORE study protocol for at least 12 months were included. Some patients (n=15) had previous panretinal laser photocoagulation. Best-corrected visual acuity and central retina thickness were recorded monthly. The foveal avascular zone and the perifoveal capillaries were quantitatively and qualitatively assessed on fluorescein angiography on two occasions during the observational period. RESULTS From the 46 eyes (46 patients) in this study, 13 (28%) had evidence of perifoveal capillary drop-out. Central retinal thickness was significantly thinner at baseline (p=0.02) and throughout the study period in these eyes compared with those with normal perifoveal capillaries. Both groups responded with a significant gain of best-corrected visual acuity to ranibizumab treatment (7.6±3.3 and 6.3±1.3 ETDRS letters, respectively). Eyes with previous panretinal laser photocoagulation displayed a comparable final outcome regarding function and morphology, requiring a similar intensity of intravitreal injections. CONCLUSIONS Perifoveal capillary drop-out did not limit the gain of visual acuity from intravitreal ranibizumab treatment. The reduction of central retina thickness was similar to that seen in eyes with normal perifoveal capillaries. Central retinal thickness in eyes with perifoveal capillary drop-out was generally reduced. However, this did not affect their benefit from treatment. Ranibizumab did not increase the amount of perifoveal capillary loss.

BACKGROUND: To report patients with age-related macular degeneration and atypical central retinal pigment epithelium (RPE) defects not attributable to geographic atrophy (GA) or RPE-tears with overlying preserved photoreceptor layers.METHODS: Multimodal imaging case-series evaluating the course of atypical RPE- defects in patients with AMD using Color fundus images, Optical coherence tomography (OCT), OCT-Angiography, fundus autofluorescence (FAF) and fluorescein-angiography (FA).RESULTS: Ten patients were identified. Three patients had a prior RPE-rip and were excluded. Seven patients with a mean follow-up period of 47 ± 38 months after the occurrence of the RPE-defect were included (age range 71-87 years). Mean distance Best corrected visual acuity (BCVA) at initial presentation was 0.36 ± 0.29logMAR and at last follow-up visit 0.51 ± 0.43logMAR. Patients presented with clinically apparent GA on funduscopy and FAF, but preserved photoreceptor layers on optical coherence tomography (OCT). On FA there was early hyperfluorescence and late pooling visible. Over time, migration of RPE/drusenoid material right above the Bruch's membrane with concomitant decrease of hypoautofluorescence was detectable in 4 cases. An enlargement of the RPE-defect was apparent in the remaining 3 cases. The majority (n = 4) showed a drusenoid pigment epithelium detachment (PED) preceding the lesion.CONCLUSIONS: Beside GA and characteristic RPE-tears, another atypical form of RPE-defect with overlying preserved photoreceptor layers are found in AMD. This so far disregarded subgroup of patients present with reasonable visual function and long-term survival of photoreceptors layers. Repair mechanisms such as ingrowth of RPE/drusenoid material and persistent subretinal fluid (SRF), but also a RPE-independent visual cycle for cone photopigment within the neurosensory retina may contribute to their favorable course.

This report provides sound evidence that the small molecule pharmaceutical PLX5622, a highly selective CSF-1R kinase inhibitor, crosses the blood-retina barrier and suppresses microglia activity. Members of this class of drug are in advanced clinical development stages and may represent a novel approach to modulate ocular inflammatory processes.

PURPOSE To compare the quality of four OCT-angiography(OCT-A) modules. METHOD The retina of nineteen healthy volunteers were scanned with four OCT-devices (Topcon DRI-OCT Triton Swept-source OCT, Optovue RTVue-XR, a prototype Spectralis OCT2, Heidelberg-Engineering and Zeiss Cirrus 5000-HD-OCT). The device-software generated en-face OCT-A images of the superficial (SCP) and deep capillary plexuses (DCP) were evaluated and scored by 3 independent retinal imaging experts. The SCP vessel density was assessed using Angiotool-software. After the inter-grader reliability assessment, a consensus grading was performed and the modules were ranked based on their scoring. RESULTS There was no significant difference in the vessel density among the modules (Zeiss 48.7±4%, Optovue 47.9±3%, Topcon 48.3±2%, Heidelberg 46.5±4%, p = 0.2). The numbers of discernible vessel-bifurcations differed significantly on each module (Zeiss 2±0.9 bifurcations, Optovue 2.5±1.2, Topcon 1.3±0.7 and Heidelberg 0.5±0.6, p≤0.001). The ranking of each module differed depending on the evaluated parameter. In the overall ranking, the Zeiss module was superior and in 90% better than the median (Bonferroni corrected p-value = 0.04). Optovue was better than the median in 60%, Topcon in 40% and Heidelberg module in 10%, however these differences were not statistically significant. CONCLUSION Each of the four evaluated OCT-A modules had particular strengths, which differentiated it from their competitors.

AIM We acquired age-matched and sex-matched Sprague-Dawley rats from 2 independent breeding establishments. Serendipitously, we observed that constitutive, and bacterial toxin-induced, expression of major histocompatibility complex (MHC) class II RT1B chain in the uveal tract was much lower in one of the cohorts. Activated microglia are known to upregulate MHC II RT1B expression during optic nerve (ON) degeneration induced by raised intraocular pressure (IOP). We investigated whether, in a model of experimental glaucoma, microglial upregulation of MHC II RT1B was less efficacious and ON degeneration correspondingly less severe in the cohort of rats with low MHC II RT1B expression. METHODS Experimental glaucoma was induced by lasering the trabecular meshwork using a standard protocol. After 2 weeks of elevated IOP, retinal ganglion cells (RGC) survival, ON degeneration, and microglial responses were determined in both cohorts of rats. RESULTS Raised IOP-induced expression of MHC II RT1B by microglia was muted in the "Low" cohort compared with the "High" cohort. Axonal degeneration, RGC loss, and microgliosis were all significantly lower in the cohort of rats with low basal and induced expression of MHC II RT1B, despite both cohorts displaying IOP responses that were indistinguishable in terms of peak IOP and IOP exposure. CONCLUSIONS Expression of MHC II RT1B by activated microglia in the ON during experimental glaucoma was associated with more severe RGC degeneration. Further studies are needed to elucidate the role of MHC II during experimental glaucoma.

PURPOSE: Optical coherence tomography angiography (OCT-A) allows noninvasive visualization of retinal vessels in vivo. OCT-A was used to characterize the vascular network of the mouse retina and was compared with fluorescein angiography (FA) and histology. METHODS: In the present study, OCT-A based on a Heidelberg Engineering Spectralis system was used to investigate the vascular network in mice. Data was compared with FA and confocal microscopy of flat-mount histology stained with isolectin IB4. For quantitative analysis the National Cancer Institute's AngioTool software was used. Vessel density, the number of vessel junctions, and endpoints were measured and compared between the imaging modalities. RESULTS: The configuration of the superficial capillary network was comparable with OCT-A and flat-mount histology in BALBc mice. However, vessel density and the number of vessel junctions per region of interest (P = 0.0161 and P = 0.0015, respectively) in the deep vascular network of BALBc mice measured by OCT-A was significantly higher than with flat-mount histology. In C3A.Cg-Pde6b+Prph2Rd2/J mice, where the deep capillary plexus is absent, analysis of the superficial network provided similar results for all three imaging modalities. CONCLUSION: OCT-A is a helpful imaging tool for noninvasive, in vivo imaging of the vascular plexus in mice. It may offer advantages over FA and confocal microscopy especially for imaging the deep vascular plexus. TRANSLATIONAL RELEVANCE: The present study shows that OCT-A can be employed for small animal imaging to assess the vascular network and offers advantages over flat-mount histology and FA.

Background. Ranibizumab is approved for treatment of macular edema in eyes with retinal vein occlusion (RVO). Some eyes show low-response to treatment with regard to visual acuity gain (VA) and OCT central retinal thickness (CRT) reduction. The goal of this study was to quantify the percentage of low-responders. Methods. Treatment of naïve eyes with macular edema secondary to RVO was included and monthly VA and CRT were analyzed. Four weeks after the loading phase, and at the end of the study, eyes were grouped into low- and good responders based on predefined criteria. The responder and low-responder groups were then compared at various time points. Results. Forty-three eyes were included. Regarding VA, 27.9% were low-responders after the loading phase and 30.2% at the end of the study. For CRT, 34.9% were low-responders after the loading phase versus 27.9% at the end of the study. 75% of patients that were VA low-responders and 73.3% of CRT low-responders after loading phase remained low-responders at the end of the study. Conclusion. Approximately 30% of patients showed low response to ranibizumab after the loading phase and after 1 year of treatment. Two-thirds of patients that were low-responders after the loading phase remained low-responders after 1 year.

Purpose: To assess the effect of a bimonthly treatment regimen with intravitreal aflibercept on retinal fluid and pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (AMD). Methods: Twenty-six treatment-naive eyes of 26 patients with choroidal neovascularisation secondary to AMD were included. The patients received three initial monthly (mean 30 days) intravitreal injections of aflibercept followed by a bimonthly (mean 62 days) fixed regimen for a total of 1 year. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) measurements were recorded at monthly intervals. In addition, the presence of intraretinal fluid (IRF) or subretinal fluid (SRF) or a combination of both as well as serous and fibrovascular PEDs were assessed. Results: The mean patient age was 80 years (range 54-93). There were 14 male and 12 female patients. The mean gain in BCVA at 1 year was 9.3 letters (SEM ±3) with a mean reduction of the central retinal thickness of 154 µm (SEM ±50). After 3 monthly injections of aflibercept, there was resolution of IRF and SRF in 80% of the treated eyes; the amount of fluid increased at months 4, 6 and 8 with troughs in between. Whereas fibrovascular PEDs remained stable after the loading phase, serous PEDs displayed a seesaw pattern. Patients without retinal pigment epithelium (RPE) atrophy at the end of the 1-year period had significantly better BCVA compared to patients with RPE atrophy (p = 0.03). Conclusion: Despite significant overall BCVA gain, bimonthly intervals seem insufficient to maintain the morphological improvements after the initial loading dose with intravitreal aflibercept.

Purpose: To assess intra- and subretinal fluid during the loading phase with intravitreal ranibizumab in exudative age-related macular degeneration and to quantify the accuracy of crosshair scan spectral-domain optical coherence tomography with regard to retinal fluid. Methods: This is a retrospective study of 31 treatment-naive patients who received 3 monthly intravitreal ranibizumab injections. Visual acuity and the presence of retinal fluid were assessed at each visit using volume and crosshair scan protocols. Results: Visual acuity improved and central retinal thickness decreased significantly during the loading phase. However, retinal fluid persisted in two thirds of the patients. The accuracy of the crosshair scan to detect fluid was 93%. Conclusions: A substantial proportion of eyes had persistent fluid after 3 months of ranibizumab injections. However, visual improvement was independent of residual fluid. Message: Crosshair scans detect relevant collections of retinal fluid accurately and may be sufficient in daily clinical practice.

PURPOSE We assessed the effects of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy on scleral architecture using spectral domain anterior segment optical coherence tomography (OCT). METHODS A total of 35 eyes of 35 patients treated with at least 30 intravitreal injections in one eye in the inferotemporal quadrant with ranibizumab or aflibercept and 10 or less intravitreal injections in the fellow eye attending the intravitreal injection clinic were included. Enhanced depth imaging anterior segment OCT was used to measure scleral thickness. For each eye the sclera was measured in four quadrants at 3 mm from the limbus. In addition axial eye length was measured in all subjects using partial coherence interferometry. RESULTS The mean number of intravitreal injections was 42 (range, 30-73) and 1.6 (range, 0-9) in the fellow eyes. In the study eyes with more than 30 injections the average scleral thickness in the inferotemporal quadrant was 568.4 μm (SD ± 66 μm) and 590.6 μm (SD ± 75 μm) in the fellow eyes with 10 or less injections (P = 0.003). The mean average scleral thickness in the other three quadrants (inferonasal, superotemporal, and superonasal) was 536.6 μm in the study eyes (SD ± 100 μm) and 545.2 μm (SD ± 109 μm) in the fellow eyes (P = 0.22). There was a borderline association of the total number of injections with scleral thickness change in the inferotemporal quadrant (r = 0.3, P = 0.052). CONCLUSIONS Intravitreal injections may lead to scleral changes when applied repeatedly in the same quadrant. Thus, alternating the injection site should be considered in patients requiring multiple intravitreal injections.

We present an unusual case of polypoidal choroidal vasculopathy (PCV) lying above the retinal pigment epithelium (RPE) in a 60-year-old Caucasian female. PCV lesions are typically located beneath the RPE layer. However, they may rarely lie above the level of the RPE due to a discontinuity in the RPE and Bruch's membrane.

Sir, Group C Streptococci are part of the human flora1 and rarely cause opportunistic infections. Here we report a case of endophthalmitis presumably caused by a cellulitis of the arm.

The neurodegenerative disease glaucoma is characterised by the progressive death of retinal ganglion cells (RGCs) and structural damage to the optic nerve (ON). New insights have been gained into the pathogenesis of glaucoma through the use of rodent models; however, a coherent picture of the early pathology remains elusive. Here, we use a validated, experimentally induced rat glaucoma model to address fundamental issues relating to the spatio-temporal pattern of RGC injury. The earliest indication of RGC damage was accumulation of proteins, transported by orthograde fast axonal transport within axons in the optic nerve head (ONH), which occurred as soon as 8 h after induction of glaucoma and was maximal by 24 h. Axonal cytoskeletal abnormalities were first observed in the ONH at 24 h. In contrast to the ONH, no axonal cytoskeletal damage was detected in the entire myelinated ON and tract until 3 days, with progressively greater damage at later time points. Likewise, down-regulation of RGC-specific mRNAs, which are sensitive indicators of RGC viability, occurred subsequent to axonal changes at the ONH and later than in retinas subjected to NMDA-induced somatic excitotoxicity. After 1 week, surviving, but injured, RGCs had initiated a regenerative-like response, as delineated by Gap43 immunolabelling, in a response similar to that seen after ON crush. The data presented here provide robust support for the hypothesis that the ONH is the pivotal site of RGC injury following moderate elevation of IOP, with the resulting anterograde degeneration of axons and retrograde injury and death of somas. Electronic supplementary material The online version of this article (doi:10.1007/s00401-011-0807-1) contains supplementary material, which is available to authorized users.