The influence of polyacrylamide gel substrate elasticity on primary cultures of rat retinal ganglion cells.

In vitro primary cell culture models of retinal ganglion cells (RGC) are widely used to study pathomechanisms of diseases such as glaucoma. The biomechanic interaction with the culture substrate is known to influence core cellular functions. RGC cultures, however, are usually grown on rigid plastic or glass substrates. We hypothesized that soft polyacrylamide gel substrates may alter survival and neurite outgrowth of primary cultured RGC. Primary retinal cultures from postnatal (day 1-6) Wistar rats were grown on glass coverslips or polyacrylamide (PA) gel substrate with different Young's elastic moduli (0.75, 10 or 30 kPa). Substrates were coated with Poly-l-lysine and/or laminin. RGC were immunostained with anti-beta-III-tubulin. Total neurite length, growth cone morphology, RGC density, mitochondrial morphology and transport as well as pro-survival pathways (Erk1/2, Akt, CREB) were assessed. PA gel substrates of E = 10 kPa significantly increased the total neurite length by factor 1.5 compared to glass (p = 0.02). The growth cone area was significantly larger by factor 5.3 on 30 kPa gels (p = 0.01). The presence of a substrate coating was more important for neurite outgrowth and RGC survival on PA gels (poly-l-lysine > laminin) than on glass. Neither mitochondrial morphology and motility nor the activation of pro-survival pathways significantly differed between the four substrates. PA gel substrates significantly enhanced RGC neurite outgrowth. The signaling cascades mediating this effect remain to be determined.

[Glaucoma Filtration Surgery - Bleb-forming Procedures]. / Filtrierende Glaukomchirurgie ­ Verfahren mit Bildung eines Filterkissens.

Glaucoma filtration surgery has been a standard surgical therapy for decades. An increasing knowledge about wound healing processes in the eye, the introduction of antimetabolite treatment and continuous improvements of the surgical technique helped making trabeculectomy - the prototype filtration surgery - a very effective therapeutic tool. However, best results will only be regularly achieved with a high level of experience and time dedicated to postoperative follow-up. Furthermore, the potential for severe early and late complications still remains high. Thus, novel stent-based filtration surgery approaches, such as the Preserflo and the XEN shunt have been introduced. This review presents these three bleb-forming filtration procedures, covering the basic principles of surgical technique, data on effectivity as well as complications.

[Cyclophotocoagulation - current applications and practical aspects]. / Zyklophotokoagulation ­ Vielfalt der Anwendungen.

Despite the advent of a large variety of minimally invasive glaucoma surgery (MIGS) techniques cyclophotocoagulation (CPC) remains a popular treatment option to lower intraocular pressure (IOP) in glaucoma patients. Guidelines for glaucoma treatment point to the rather unphysiological mode of action and, thus, recommend CPC mainly for refractory glaucoma and/or eyes with limited visual potential. The primary target of CPC is the pigmented secretory ciliary body epithelium resulting in a decreased production of aqueous humor. In addition, an increase of aqueous outflow may contribute to the IOP lowering. CPC is generally considered a low risk intervention. However, macular edema, prolonged intraocular inflammation, vision loss, hypotony, pain or phthisis occur at considerable rates. Over the past decades new promising modes of cyclophotocoagulation have evolved aiming at reducing the risk of adverse effects and improving the efficiency. This article provides an overview of the different currently available cyclophotocoagulation modes: Besides the classic transscleral continuous-wave cyclophotocoagulation it covers endoscopic cyclophotocoagulation, micropulse transscleral laser treatment and transscleral controlled cyclophotocoagulation. Various practical aspects of the treatment in light of the current literature are being discussed.

Current Practice in the Treatment of Epithelial and Melanocytic Tumours with Interferon-α2b: A Survey of Tertiary Eye Centres in Germany.

PURPOSE: To evaluate the standard of care, in particular the use of topical or subconjunctival interferon-α2b, in treating ocular surface squamous neoplasia or melanocytic tumours in tertiary eye centres in Germany. METHODS: A survey containing 14 questions was sent to 43 tertiary eye centres in Germany. The questions addressed the surgical and medical management of ocular surface squamous neoplasia and melanocytic tumours (primary acquired melanosis and malignant melanoma), as well as the clinical experiences and difficulties in prescribing off-label interferon-α2b eye drops and subconjunctival injections. RESULTS: Twenty-four tertiary eye centres responded to the survey. Eighty-three percent of centres had used interferon-α2b in their clinical practice and 25% prescribed it as the first-line cytostatic agent following surgical excision of ocular surface squamous neoplasia, while 10% would do so for melanocytic tumours. Correspondingly, the majority of respondents selected mitomycin C as their first-line agent. Side effects were uncommon with topical interferon-α2b eye drops but were more frequently reported after subconjunctival interferon-α2b injections. In total, eight centres had experience with interferon-α2b injections. The most significant obstacles perceived by ophthalmologists when prescribing interferon-α2b were its high cost and the reimbursement thereof. CONCLUSION: Off-label mitomycin C was the preferred adjuvant therapy for epithelial and melanocytic tumours, with interferon-α2b being the standard second-line option. Interferon-α2b has predominantly been used to treat ocular surface squamous neoplasia and, to a lesser extent, melanocytic tumours at German tertiary eye centres. Following its market withdrawal, supply shortages of interferon-α2b are likely to have a profound impact on patient care and their quality of life.

On the Current Care Situation and Treatment of Ocular Mucous Membrane Pemphigoid in Germany. / Zur Versorgungssituation und konservativen Therapie des okulären vernarbenden Schleimhautpemphigoids in Deutschland.

BACKGROUND: Ocular involvement in mucous membrane pemphigoid (MMP) is relatively rare, with a prevalence of 25 cases per million population, equating to approx. 2,100 patients throughout Germany. Diagnosis can be difficult - especially in cases of isolated ocular involvement - and treatment can be complex and lengthy. Immunosuppressants or immunomodulatory drugs are often used. Due to the complexity of diagnosis and treatment, MMP patients are usually referred to specialized centers. The aim of this project was to evaluate the current care situation of patients with ocular MMP in Germany. METHODS: A paper-based survey was designed and sent to all university eye clinics and other specialized centers in Germany in April 2020. The survey asked about the existence of a specialized outpatient service, the total annual number of patients with MMP, the annual number of newly diagnosed patients, any interdisciplinary collaboration for diagnostic or therapeutic purposes, as well as the local and systemic therapy used. RESULTS: Of a total of 44 clinics, 28 (64%) responded, reporting a total average of 27 ± 42 (0 - 200) patients and 3.6 ± 2.2 (0 - 10) new cases per year. This corresponds to a total of 741 patients. Only nine (32%) of the responding clinics offer specialized MMP clinics. 93% of the centers collaborate with the local dermatology department. 79% perform serological and histological diagnostics in-house. About half of the centers (n = 16) apply a standardized treatment regime. Systemic glucocorticoids (66.7%) are most commonly used, followed by mycophenolate mofetil and dapsone (57.1%), rituximab (33.3%), azathioprine and cyclophosphamide (28.6%), as well as methotrexate (19.0%). The least frequently used treatment is intravenous immunoglobulin (14.3%). CONCLUSION: This survey of German ophthalmology departments obtained data from about one third of the estimated total cohort of all patients with MMP in Germany. These are presumed to be exclusively patients with at least one ocular involvement. The complex care of these patients is usually provided in collaboration with a dermatologist and with the use of systemic anti-inflammatory medication. Currently, an ophthalmological MMP register is being established to better record the epidemiology and care situation of this rare disease in Germany and to improve it in the long term.

Endocrine Dysfunction in Open Angle Glaucoma. / Endokrine Auffälligkeiten beim Offenwinkelglaukom.

The eye, like all organs, is exposed to the effects of the body's endocrine system. In addition, however, local branches of the endocrine system control important organ-specific functions, such as the production and drainage of aqueous humour. Similarly, the eye as a sensory organ acts back on endocrine controlled functions of the body, for example the day-night rhythm. This article aims to illustrate the physiological and pathological interactions of the eye and the endocrine functions of the body in the context of glaucoma. 1. The renin-angiotensin-aldosterone system, which as a local system is involved in the control of aqueous humour production and outflow. 2. The hormone endothelin, which as a strong vasoconstrictor plays a role in the dysregulated perfusion of the optic nerve and retina, and 3. the disruption of the day-night rhythm in advanced glaucoma, which is thought to be caused by damage to light-sensitive ganglion cells.

Reorganization of the perifoveal microvasculature after macular hole closure assessed via optical coherence tomography angiography.

PURPOSE: To quantify short-term microvascular changes after pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling in patients with idiopathic macular hole (IMH) using optical coherence tomography angiography (OCTA). DESIGN: Cohort Study. PARTICIPANTS: This study included patients with IMH. Affected eyes were compared with fellow eyes. METHODS: 6 × 6 mm OCTA (Zeiss Angioplex, Zeiss Meditec, Dublin, CA, USA) images of the study eye and fellow eye were acquired one day before surgery, 4 weeks and 12 weeks after surgery. Microvascular alterations in the superficial and deep capillary plexus were assessed by measuring vessel density and the shortest distance to the surrounding vessels of all intercapillary pixels. Only vessels enclosed by an ETDRS Grid centered on the fovea were analyzed. MAIN OUTCOME MEASURES: Change of vessel density and vessel distance to baseline. RESULTS: OCTA images of the 15 study and 15 fellow eyes of 15 included patients (mean ± SD of age: 67.89 ± 5.2 years) were analyzed and revealed a significant increase in vessel density and decrease in vessel distance of the deep capillary plexus in study eyes 4 weeks after surgery compared to baseline. Our superficial capillary plexus findings were the inverse, namely a significant decrease in vessel density and increase in vessel distance. Postoperative microvascular changes proved to be closely associated with the extent of retinal thickness reduction in the perifoveal deep capillary plexus. CONCLUSIONS: IMH closure after PPV and ILM peeling caused a significantly improved microvasculature in the deep capillary plexus, which may represent reorganized perifoveal microvasculature due to the regression of cystoid spaces.

[Glaucoma Surgery in Anterior Segment Dysgeneses]. / Glaukomchirurgie bei Vorderabschnittsdysgenesien.

Anterior segment dysgeneses are rare conditions, and mostly occur sporadically. The severity of dysgenesis and the number of structures affected are highly variable. Glaucoma occurs in approximately 50% of all patients, either as part of primary chamber angle dysgenesis or secondary to surgery, mostly for removal of congenital cataracts. This review provides a brief overview of the embryological background and the spectrum of phenotypes, such as primary congenital glaucoma, Axenfeld Rieger and Peters Anomaly. Current surgical approaches to lower intraocular pressure are discussed. Special attention is paid to the increasingly used microcatheter-assisted 360° trabeculotomy and glaucoma drainage devices in paediatric glaucoma surgery.

[Non-arteritic Anterior Ischaemic Optic Neuropathy: Pathogenesis and Therapeutic Approaches]. / Pathogenese und Therapie der nicht arteriitischen anterioren ischämischen Optikusneuropathie.

Non-arteritic anterior ischemic optic neuropathy (NAION) is an acute neurodegenerative disease with a largely elusive early pathogenesis and no specific therapy. Recent data from animal models of the disease as well as from epidemiological studies have provided new insights into the disease mechanism of NAION. On the basis of this new knowledge, a broad variety of therapeutic approaches is currently being evaluated in animal and clinical studies. This review aims to provide an overview of the pathogenesis as well as neuroprotective therapeutic concepts of recent and currently running studies.

Functional assessment of the aqueous humour distal outflow pathways in bovine eyes using time-of-flight magnetic resonance tomography.

The major part of the aqueous humor leaves the eye through the "conventional outflow pathway", consisting of the trabecular meshwork, Schlemm's canal, collector channels, an intrasceral plexus and the episcleral veins. While the trabecular meshwork is well characterized, little is known about anatomical and functional features of the peripheral outflow tract beyond Schlemm's canal. The emergence of minimally-invasive glaucoma surgery directly targeting the outflow resistance in the trabecular meshwork has elicited growing interest in these structures. We used time-of-flight magnetic resonance imaging in ex vivo bovine eyes to map fluid flow under physiological conditions. We were able to identify the peripheral outflow vessels solely by the signal detected from the fluid flow inside their lumina. A question of clinical relevance is, whether localized opening of the trabecular meshwork leads to only localized or to a 360° increase in intrascleral flow. To address this, a goniotomy ab interno was performed in 3 eyes and the flow signal intensity was quantified sectorially. A significant increase in fluid flow was observed in the sector distal to the goniotomy (p = 0.0005) but not in the other sectors (p = 0.1). As a proof of concept we demonstrated that TOF-MRI based detection of flow in the peripheral aqueous outflow tract is feasible. The functional link observed between trabecular meshwork sectors and their distal outflow tract sectors may be relevant for minimally-invasive glaucoma surgery in humans.

Trabeculotomy opening size and IOP reduction after Trabectome® surgery.

BACKGROUND: Trabeculotomy with the Trabectome® is an effective surgical procedure to lower intraocular pressure (IOP). However, in some patients it does not lead to a significant IOP reduction despite a gonioscopically well visible opening of Schlemm's canal. This study investigated whether the size of the trabeculotomy opening and other parameters, including anterior chamber depth (ACD) are related to IOP reduction. METHODS: Retrospective observational case series with 93 eyes of 93 patients who underwent Trabectome surgery. Trabeculotomy opening and ACD were measured with an anterior segment swept source OCT. IOP was taken pre-operatively and at a single follow-up visit [follow-up time 125 ± 66 days (mean ± SD)]. The relationship between IOP reduction and OCT parameters and possible confounding factors was analyzed in a multiple linear regression model. RESULTS: The trabeculotomy opening size did not correlate with IOP reduction (slope of regression line = 0.0016; 95% confidence interval of slope: -0.025 to 0.028). The same applied for all other parameters tested, including ACD, which showed a tendency towards better IOP reduction with a deeper AC (slope = -1.9; 95% confidence interval: -5.54 to 1.73). Comparison between the 1st and 4th quartile of the trabeculotomy opening showed a significantly higher ACD in the largest trabeculotomy opening quartile (3.32 ± 0.05 mm vs. 3.16 ± 0.04 mm; p = 0.031). CONCLUSIONS: The fact that the trabeculotomy opening size did not correlate with IOP reduction points to the poorly understood role of the intrascleral aqueous outflow pathway in glaucomatous IOP elevation. A deeper AC might be a factor promoting a larger trabeculotomy opening.

Risk of progression in macula-on rhegmatogenous retinal detachment.

PURPOSE: To identify factors that may lead to a rapid progression in macula-on rhegmatogenous retinal detachment (RRD), in particular, those that may lead to macular involvement. METHODS: Observational, prospective, single-center study. Patients referred for surgery due to primary rhegmatogenous retinal detachment with the macula on between 2009 and 2013 were included. Relevant factors analyzed included age, time delay until surgery, lens status, myopia, the detachment's location and configuration as well as number, size and type of retinal breaks. Eyes underwent optical coherence tomography to detect macular detachment. A multivariate analysis was performed to investigate the effect of several factors in the progression of retinal detachment. RESULTS: A total of 116 eyes of 116 patients were included. Mean time delay between admission and surgery was 1.8 ± 1.4 days. Progression was observed in 19.8% of the eyes. Of those, 47.8% presented macular detachment. Ten of the 11 (90.9%) eyes presenting progression involving the macula also exhibited a bullous configuration, which was the only parameter that correlated significantly with detachment progression in patients with (p = 0.0036) and without (p = 0.0014) macular involvement. CONCLUSIONS: For the first time in a prospective trial, a bullous configuration was found to be a highly significant predictor for progression in macula-on detachments. Our data support prompt surgery in patients diagnosed with bullous macula-on RRD.

Current Status and Future Perspectives of Optic Nerve Imaging in Glaucoma.

Being the primary site of degeneration, the optic nerve has always been the focus of structural glaucoma assessment. The technical advancements, mainly of optical coherence tomography (OCT), now allow for a very precise quantification of the optic nerve head and peripapillary retina morphology. By far the most commonly used structural optic nerve parameter is the thickness of the parapapillary retinal nerve fiber, which has great clinical utility but also suffers from significant limitations, mainly in advanced glaucoma. Emerging novel imaging technologies, such as OCT angiography, polarization-sensitive or visible-light OCT and adaptive optics, offer new biomarkers that have the potential to significantly improve structural glaucoma diagnostics. Another great potential lies in the processing of the data already available. Artificial intelligence does not only help increase the reliability of current biomarkers but can also integrate data from various imaging modalities and other clinical measures to increase diagnostic accuracy. And it can, in a more efficient way, draw information from available datasets, such as an OCT scan, compared to the current concept of biomarkers, which only use a fraction of the whole dataset.

Trabectome surgery for primary and secondary open angle glaucomas.

PURPOSE: In most forms of open angle glaucoma, the trabecular meshwork is the main barrier for aqueous humor outflow, causing elevated intraocular pressure (IOP). The Trabectome is a minimal invasive device for the surgical treatment of open angle glaucoma, particularly eliminating the juxtacanalicular meshwork. This study was conducted to compare the effectiveness and complication profile among different glaucoma subgroups. METHODS: Single center prospective observational study. There were 557 consecutive eyes of 487 patients included in this study. Trabectome surgery was performed either alone or in combination with cataract surgery. Intraoperative and postoperative complications were documented systematically. Main outcome measures were IOP reduction over time and the preoperative and postoperative number of IOP-lowering medications. Due to subgroup sizes, only data from eyes with primary open angle glaucoma and pseudoexfoliation glaucoma were processed for statistical analysis. RESULTS: For the 261 eyes classified as primary open angle glaucoma, preoperative IOP was 24 ± 5.5 mmHg (mean ± SD) under 2.1 ± 1.3 IOP-lowering medications. After a mean follow-up of 204 ± 238 days, IOP was reduced to 18 ± 6.1 mmHg, and medication was reduced to 1.2 ± 1.1. For the 173 eyes classified as pseudoexfoliation glaucoma, after a mean follow-up of 200 ± 278 days, IOP was reduced from 25 ± 5.9 mmHg to 18 ± 8.2 mmHg, and medication was reduced from 2.0 ± 1.2 to 1.1 ± 1.1. A Cox proportional hazards model hinted forward superiority of the combined surgery cases (Trabectome + Phaco + intraocular lens) in comparison to Trabectome surgery only in phakic or pseudophakic eyes. No serious complications were observed. CONCLUSIONS: Minimal invasive glaucoma surgery with the Trabectome seems to be safe and effective. The subgroup analysis of different kinds of open angle glaucomas presented in this study may help in first-line patient selection. The lack of ocular surface alterations makes it a valuable addition to glaucoma surgery.

[Nonarteritic anterior ischemic optic neuropathy (nAION)]. / Nichtarteriitische anteriore ischämische Optikusneuropathie (nAION).

Nonarteritic anterior ischemic optic neuropathy (nAION) is the second most common degenerative disease of the optic nerve. The pathogenesis remains elusive. A transient ischemia in the short posterior ciliary arteries not triggered by thromboembolic events is suspected. The typical history of a sudden onset of scotoma without associated pain in conjunction with (sectorial) optic disc swelling, an afferent pupillary defect and a visual field defect are of decisive diagnostic importance. The most urgent diagnostic measure is the exclusion of arteritic AION. There are no proven treatment approaches. Frequently used but without clear study results, is the treatment with steroids and secondary prophylaxis with acetylsalicylic acid (ASA). Recurrence in the ipsilateral or contralateral eye is possible.

Evaluation of intraocular pressure elevation in a modified laser-induced glaucoma rat model.

The main drawbacks of currently described pressure induced glaucoma animal models are, that intraocular pressure (IOP) either rises slowly, leading to a heterogeneous onset of glaucoma in the treated animals or that IOP normalizes before significant damage occurs, necessitating re-treatment. Furthermore, a variable magnitude of IOP increase often results when particles are introduced into the anterior chamber. In order to develop a simple and reproducible rat glaucoma model with sustained IOP elevation after a single treatment we induced occlusion of the chamber angle by anterior chamber paracentesis and subsequent laser coagulation of the limbal area with 35, 40 or 45 laser burns. Right eyes served as controls. IOP was measured three times weekly using TonoLab rebound tonometry in awake animals. After four weeks, retinal tissue was harvested and processed for whole mount preparation. The number of prelabeled, fluorogold-positive retinal ganglion cells (RGCs) was analyzed under a fluorescence microscope. The eyes were further analyzed histologically. Results are expressed as means and standard deviation. Amplitude and duration of the IOP elevation increased with the number of laser burns. Two weeks after 35, 40 or 45 translimbal laser burns the IOP difference between treated and control eye was 7.5 ± 5, 14 ± 8 or 19 ± 9 mmHg, respectively; the RGC density/mm(2) 28 days after treatment was 1488 ± 238 for control eyes (n = 31) and 1514 ± 287 (n = 10), 955 ± 378 (n = 10) or 447 ± 350 (n = 11) for the respective laser groups. Mean IOP of all control eyes over the observation period was 12.4 ± 0.8 mmHg. The chamber angle showed pigment accumulation in the trabecular meshwork of all laser groups and confluent peripheral anterior synechia after 40 and 45 laser burns. Histologic examination of the retina revealed increasing glia activation in a pressure dependant manner. In this study, >91% of laser treated rats developed secondary glaucoma with sustained IOP elevation for at least 2 weeks. The amount of IOP elevation and RGC loss correspond with the number of laser burns applied. This relatively high success rate after a single procedure may constitutes an advantage over established glaucoma models, as this decreases the risk of complications (e.g. corneal decompensation, intraocular bleeding or inflammation) and, thus, improves the outcome.

Risk Factors for Severe Bleeding Complications in Glaucoma Surgery and the Role of Antiplatelet or Anticoagulant Agents.

Purpose: To evaluate the influences and risk factors for severe bleeding complications during glaucoma surgery, and to investigate the role of antiplatelet (AP) and anticoagulant (AC) agents. Methods: This prospective study enrolled patients undergoing trabeculectomy, trabeculotomy (with Trabectome® or Kahook Dual Blade®), viscocanaloplasty and Ahmed or Baerveldt implants. Bleeding severity was graded on an ordinal scale ranging from 0 to 5. Immediately after surgery and one day later, the incidence and severity of bleeding events was documented on a standardized form. A grade ≥3 was defined as severe bleeding. The influence of known systemic disorders, the type of anesthesia, surgical procedure, intraoperative blood pressure, and the use of or change in AP or AC agents on intraoperative bleeding were analyzed. Results: Data from 89 eyes undergoing glaucoma procedures were included (age 71.3y ± 10.5). We observed severe intraoperative bleeding in 8 eyes (9%) and found that concomitant diseases such as the history of a deep vein thrombosis or peripheral arterial occlusive disease, and the type of surgical procedure (trabeculectomy and viscocanaloplasty) were significantly associated with severe bleeding events. By contrast, the use of AP/ AC agents had no significant influence on severe intraoperative bleeding events. Conclusion: According to the results of our study cohort, glaucoma procedures entailing scleral manipulations (trabeculectomy and viscocanaloplasty) and concomitant diseases such as the history of a deep vein thrombosis or peripheral arterial occlusive disease influence the risk of severe intraoperative bleeding events, we detected no increased risk related to concomitant antiplatelet and/ or anticoagulant medication use.

The expression of dynein light chain DYNLL1 (LC8-1) is persistently downregulated in glaucomatous rat retinal ganglion cells.

High intraocular pressure induces glaucomatous degeneration of retinal ganglion cells (RGCs). The cellular mechanisms leading to activation of the apoptosis cascade are multidimensional and only partially understood. A small dynein subunit, the light chain DYNLL1 (synonym LC8-1, PIN) has recently been shown to be an important regulator of neuron proteins known to be involved in glaucomatous RGC death including NO synthases, the pro-apoptotic protein Bim and the dynein intermediate chain. Also, DYNLL1 is a regulator of mitochondria anchorage in axons, which is impaired in glaucoma. We investigated expression of DYNLL1 and 2 and its dynein binding partner dynein intermediate chain in a rat model of chronic glaucoma. Laser capture microdissection (LCM) allowed us to collect distinct cell layers and cell bodies from the retina to gain data highly specific for retinal ganglion cells. Glaucoma was induced in 23 rats by laser treatment to the aqueous outflow tract. RNA was extracted from LCM dissected ganglion cell layers (GCL) and 100 pooled RGCs per retina. Expression levels for 1, 2 and 4 week timepoints were analysed by quantitative PCR for DYNLL1 and 2, dynein intermediate chain and GFAP. DYNLL protein abundance in RGCs was quantified in immunostained retina sections. DYNLL gene 1 but not 2 was expressed in RGCs. In the glaucoma model DYNLL1 was strongly and persistently downregulated at all timepoints. DYNLL protein was significantly less abundant at the 4 week timepoint. In contrast, the motorprotein binding partner dynein intermediate chain 1 was more stably expressed. DYNLL2 was upregulated in glia cells at 2 weeks. Expression of DYNLL1, the only form of the dynein light chain expressed in RGCs, is downregulated persistently in glaucoma, while its binding partner dynein IC-1 is unchanged. The specific lack of DYNLL1 could have an impact on the function of their regulatory binding partners and contribute in several ways to neuron dysfunction and apoptosis.

Reliability of Subjective Assessment of Spectral-Domain OCT Pathologic Features by Multiple Raters in Retinal Vein Occlusion.

Purpose: To examine the interrater and intrarater reliability of qualitatively and quantitatively assessed disorganization of retinal inner layers (DRIL) and disorganization of retinal outer layers (DROL) by multiple raters. Subjectively assessing these surrogate biomarkers can be challenging in daily routine, despite the high resolution of spectral-domain (SD) OCT scans. Design: Retrospective trial. Participants: Three hundred six pooled SD OCT scans of 34 patients treated for macular edema caused by retinal vein occlusion (RVO) between January 2016 and December 2017. Methods: SD OCT scans were assessed by 6 raters regarding presence of cystoid macular edema, subretinal fluid (SRF), vitreoretinal traction, and epiretinal membrane and extent of DRIL and DROL. Main Outcome Measures: Interrater and intrarater reliability were calculated applying κ statistics for qualitative assessment regarding each pathologic feature's presence in all evaluated OCT scans, and for quantified horizontal DRIL and DROL extent within each OCT cross-section. Results: Cystoid macular edema and SRF assessments revealed excellent inter- and intrarater reliability with almost perfect strength of agreement, whereas subjective DRIL and DROL evaluations yielded low κ statistics with slight to moderate strength of agreement. Furthermore, the presence of SRF remarkably compromised the reliability of DROL detection. Conclusions: Our data highlight the limited subjective assessibility of DRIL and DROL, underscoring the need for automated image analysis to improve the reliability of OCT biomarkers for clinical studies and daily practice.

Risk Factors for Severe Bleeding Complications in Vitreoretinal Surgery and the Role of Antiplatelet or Anticoagulant Agents.

PURPOSE: To evaluate the influences and risk factors for severe bleeding complications during vitreoretinal surgery and to investigate the role of antiplatelet and anticoagulant agents. DESIGN: Prospective trial. PARTICIPANTS: Patients undergoing vitreoretinal surgery. METHODS: The procedures included were pars plana vitrectomy and scleral buckling. We developed a uniform classification to grade the bleeding severity. Bleeding was graded on an ordinal scale ranging from 0 to 5. Immediately after surgery and 1 day later, the incidence and the severity of bleeding events was documented on a standardized form. A grade of 3 or more was defined as severe bleeding. Furthermore, the influence of known systemic disorders before surgery, the type of anesthesia, type of surgical procedure, intraoperative blood pressure, and the use or change of antiplatelet or anticoagulant agents on intraoperative bleeding was analyzed. MAIN OUTCOME MEASURES: Incidence and risk factors for severe intraoperative bleeding events. RESULTS: Data from 374 eyes undergoing vitreoretinal procedures were included in our study (mean age, 67.6 ± 12.9 years). A severe intraoperative bleeding event was observed in 15 eyes (4%). We found that concomitant diseases such as diabetes mellitus and carotid artery stenosis, the presence of diabetic retinopathy, younger age, and scleral buckling combined with a transscleral puncture were associated significantly with severe bleeding events. By contrast, use of antiplatelet or anticoagulant agents, or both, had no significant influence on severe intraoperative bleeding events. CONCLUSIONS: Although external manipulations during buckling surgery (e.g., drainage of subretinal fluid) and concomitant diseases such as diabetes mellitus and carotid artery stenosis influences the risk of severe intraoperative bleeding events, we did not detect an increased risk related to coexisting antiplatelet or anticoagulant medication use, or both.