The formation of ubiquitin rich condensates triggers recruitment of the ATG9A lipid transfer complex to initiate basal autophagy.

Autophagy is an essential cellular recycling process that maintains protein and organelle homeostasis. ATG9A vesicle recruitment is a critical early step in autophagy to initiate autophagosome biogenesis. The mechanisms of ATG9A vesicle recruitment are best understood in the context of starvation-induced non-selective autophagy, whereas less is known about the signals driving ATG9A vesicle recruitment to autophagy initiation sites in the absence of nutrient stress. Here we demonstrate that loss of ATG9A or the lipid transfer protein ATG2 leads to the accumulation of phosphorylated p62 aggregates in the context of basal autophagy. Furthermore, we show that p62 degradation requires the lipid scramblase activity of ATG9A. Lastly, we present evidence that poly-ubiquitin is an essential signal that recruits ATG9A and mediates autophagy foci assembly in nutrient replete cells. Together, our data support a ubiquitin-driven model of ATG9A recruitment and autophagosome formation during basal autophagy.

[Laser membranotomy in the management of acute premacular hemorrhage : Case report and overview on the approach]. / Lasermembranotomie beim Management einer akuten prämakulären Blutung : Fallvorstellung und Überblick zum Vorgehen.

Acute premacular bleeding is often associated with vasoproliferative retinal changes, vascular anomalies or a Valsalva maneuver. The diagnosis is made during the funduscopic examination and can if necessary be confirmed with optical coherence tomography (OCT). This article presents a case example with a sub-inner limiting membrane (ILM)/sub-hyaloidal bleeding. Furthermore, we present various treatment options and give an overview on the use of the Nd:YAG laser for laser membranotomy as a minimally invasive treatment option with a low complication profile.

[The role of the vitreous in the pathogenesis of age-related macular degeneration]. / Der Einfluss des Glaskörpers auf die Pathogenese der altersabhängigen Makuladegeneration.

Age-related macular degeneration (AMD) is the main cause of severe visual decease in elderly people in the industrialised countries. AMD is a multifactorial disease with only limited therapeutic options before anti-VEGF treatment was introduced. In spite of all the progress no long-term healing is possible. Actually, the vitreous is being investigated as a possible co-factor in the pathogenesis of AMD. Numerous authors demonstrated a higher incidence of vitreoretinal adhesion in exudative AMD by considering age, genetic and environmental factors. The essential question is whether the therapeutic release of vitreoretinal adhesion could affect the development and progress of AMD. Up to now only case reports and case series have demonstrated a positive effect on disease progress. An ongoing multicentre, prospective, comparative, randomised, double-blind clinical trial with enzymatic vitreolysis is now evaluting the effect of vitreoretinal release on the progress of AMD. The results are necessary to evaluate whether vitreoretinal release is a therapeutic option for the future.

[Massive subretinal bleeding--treat it or leave it?]. / Massive subretinale Blutung bei AMD am letzten Auge - behandeln oder nicht?

In eyes with massive subretinal haemorrhages, ambulatory vision can be achieved by pars plana vitrectomy and subretinal surgery. In patients with only one functional eye, this treatment is important to preserve the quality of life. The resulting large pigment epithelial defect limits visual rehabilitation. For the same reason, rTPA/gas injection or a macular translocation are possible but not sufficient in these cases.

[Anatomical and functional results after macular hole surgery]. / Anatomische und funktionelle Ergebnisse nach Makulaforamenchirurgie.

BACKGROUND: In a retrospective study we examined the anatomical and functional effects of a combined macular hole surgery with and without the application of indocyanin green (ICG) as well as phacoemulsification. METHODS AND PATIENTS: Out of 91 patients (91 eyes) with idiopatic macular holes 82 eyes were phacic. 25 cases received during the first surgery a combined pars plana vitrectomy with phacoemulsification. In 46 eyes the vitrectomy and consecutive peeling of the inner limiting membrane (ILM) was performed without ICG (Group A), in 45 eyes with ICG-assisted staining of the ILM (Group B). The average follow-up time was 19 months (12 - 24 months). RESULTS: The primary closure rate was 82.4 % and 94.5 % after reoperation. In Group A there were primarily 76 % and at the end 89.1 % closed results compared with 88.9 % and 100 % in group 2 (p = 0.172). Five persisting holes had a preoperative diameter above 600 microm (p = 0.014). Visual acuity improved in Group A preoperatively from 0.17 to postoperatively 0.33 and in Group B from 0.22 to postoperatively 0.38. The difference between both groups was not significant (p = 0.106). From 82 phacic eyes 25 were treated by a combined vitrectomy with phacoemulsification, 23 eyes received later a phacoemulsification while 34 remained phacic. DISCUSSION: Peeling of the ILM was complete after staining with ICG resulting in an increased closure rate. The functional results between both groups did not differ significantly. Phacic eyes may keep their clear lens even after multiple surgeries.

[Glaucoma drainage system according to Molteno for therapy-resistant glaucoma--a two-stage surgical technique to avoid postoperative hypertension]. / Glaukomdrainagesystem nach Molteno bei therapieresistentem Glaukom--eine zweizeitige Operationstechnik zur Vermeidung einer postoperativen Hypotonie.

BACKGROUND: The treatment of therapy-resistant secondary glaucoma with cyclodestructive approaches may give rise to unsatisfactory intraocular pressure results, leading to phthisis. A final option may be the implantation of an external glaucoma drainage system (GDS). A consecutive positioning of the drainage system under the conjunctiva and implantation of the drainage tube into the anterior chamber, may result in an uncontrolled reduced of intraocular pressure leading to intraocular haemorrhages into the anterior chamber or vitreous cavity. In particular, expulsive haemorrhages are feared as deleterious complication. PATIENTS AND METHODS: 15 patients (15 eyes) with secondary glaucoma received a GDS. All patients were previously unsuccessfully treated by numerous approaches (mean 2.7 times). The mean preoperative intraocular pressure was 37 mmHg (range: 22 to 55 mmHg). We performed a sequential approach: during the first operation we implanted and fixed the resorption site of a Molteno GDS onto the sclera close to the equator in the superotemporal quadrant. After an inflammation-free interval of 2 - 3 weeks we placed the drainage tube into the anterior chamber. The average postoperative follow-up period was 20.5 months (range: 3 to 62 months). RESULTS: The implantation of the GDS using a sequential approach was well tolerated by all patients. While 14 out of 15 eyes achieved an IOP of 15 mmHg (range: 12 to 18 mmHg), 2 of them still required additional topical glaucoma treatment. An unsatisfactory IOP regulation was observed in only one eye although a revision surgery was performed postoperatively. Four eyes developed a light anterior chamber haemorrhage that resorbed without serious complications within 3 weeks. A choroidal effusion in one eye was treated by an anterior chamber injection of a viscoelastic gel. CONCLUSION: The potential disadvantage of the GDS can be almost completely avoided using a sequential approach. The implant heals well in the subtenon space during the first postoperative week, thus preventing an overfiltration of anterior chamber fluid. Our positive results show that the GDS is an important treatment option in selected patients.

[Pars-plana vitrectomy with anterior chamber infusion via a paracentesis in pseudophakic eyes]. / Pars-plana-Vitrektomie mit Infusionszugang über eine korneale Parazentese bei pseudophaken Augen.

BACKGROUND: More than 50% of vitrectomies are performed in pseudophakic eyes. There is free communication between the anterior segment of the eye and the vitreous cavity through the zonular fibres of the lens. This means it is possible to use a primary anterior chamber infusion for pars-plana vitrectomy. METHODS: For some years, therefore, we have used an anterior chamber approach for the infusion cannula when carrying out such simple vitreo-retinal procedures as silicone oil removal or macular pucker peeling in pseudophakic eyes. RESULTS: In all eyes the anterior chamber access was placed via a corneal paracenthesis and during all vitrectomies it was held in place by corneal tissue tone with no need for suturing. Secure wound closure was also achieved without suturing by simply swelling the paracentesis. Conventional sclerotomies were closed with absorbable sutures. During vitrectomy the infusional flow was sufficient to ensure adequate intraocular pressure regardless of intraocular lens type and diameter. CONCLUSIONS: In pseudophakic eyes the anterior chamber infusion approach by way of a paracentesis is a safe way of reducing surgical trauma during vitrectomy. It must, however, be borne in mind that when an endotamponade is applied it is necessary to switch the infusion to one of the sclerotomies.

Complete resorption of retinal hemorrhages in idiopathic thrombocytopenic purpura.

PURPOSE: Idiopathic thrombocytopenic purpura (ITP) is characterized by refractory thrombocytopenia, production of autoantibodies, and persistent predisposition to bleeding affecting virtually all mucocutaneous tissues and various organs. METHODS: A 50-year-old man with chronic ITP and diabetic maculopathy developed massive preretinal, intraretinal, and numerous subretinal hemorrhages accompanied by impaired vision to 20/400. His platelet count was 1100/microL, hemoglobin concentration was 4.6 mg/dL, however his blood clotting and activated partial thromboplastin time (APTT) maintained a normal 26 sec. RESULTS: After a splenectomy the patient was placed on high-dose oral corticosteroids (40 mg/day), immunoglobulin, and CellCept. The platelet count was restored to 25,000/microL within months. Four months later the unaffected retina received a panretinal photocoagulation and intravitreal triamcinolone injection (25 mg). Two years after the thrombolytic event the hemorrhages resolved completely and the patient's vision recovered to 20/100. CONCLUSIONS: Repetitive treatments with immunoglobulins and high-dose corticosteroids may increase the platelet count, inducing a complete resorption of the retinal hemorrhages and visual recovery during a long-term follow-up.

High incidence of vitreomacular traction in recurrent choroidal neovascularisation after repeated photodynamic therapy.

BACKGROUND: The causes of recurrent choroidal neovascularisation (CNV) after photodynamic therapy (PDT) remain controversial. Subretinal surgery was carried out after unsuccessful PDT. AIMS: To determine intraoperatively the status of the posterior vitreous interface. DESIGN: Interventional case series. METHODS: Conventional three-port vitrectomy was carried out in 10 eyes with CNV that had undergone 1-4 PDT sessions. The vitreous cutter was held close to the edge of the optic nerve to evaluate the status of the posterior vitreous. RESULTS: Lesion size showed an increase from 1.5 (standard deviation (SD) 0.53) to 2.3 (SD 0.83) macular photocoagulation study disc diameters, between the first and the last PDT. Intraoperative findings during vitrectomy showed little liquefaction of the vitreous gel and an incomplete posterior-vitreous detachment, with remarkably firm attachments at the macula in all cases (10/10). CONCLUSION: We determined an abnormally high incidence of vitreous attachments in eyes with recurrent CNV. Vitreomacular attachments may trigger the progression or recurrence of CNV.

Lidocaine-assisted xylocaine jelly anesthesia versus one quadrant sub-Tenon infiltration for self-sealing sclerocorneal incision routine phacoemulsification.

PURPOSE: To compare the effect of xylocaine jelly and intracameral lidocaine with one quadrant instant sub-Tenon infiltration for self-sealing sclerocorneal phacoemulsification. METHODS: One hundred patients were enrolled into a prospective randomized study, receiving either a combination of topical 2% xylocaine jelly and 0.5 ml of intracameral 1% lidocaine or sub-Tenon infiltration with 2 ml of 2% xylocaine on the operating table. All patients underwent a standard divide and conquer phacoemulsification procedure through a superior sclerocorneal frown incision followed by implantation of a polymethylmethacrylate intraocular lens. Intraoperative pain was indicated by the patient by squeezing the bedside nurse's hand, who allocated it to particular stages of surgery on a chart. After surgery, patients assessed the pain experienced using a 10-unit visual analogue scale. RESULTS: Pain was indicated on 31 occasions during the operation in the sub-Tenon group (mainly the injection itself) and 67 times in the topical group. The median overall subjective pain score was 3 in the jelly group and 0 in the sub-Tenon. Five eyes (10%) had to be converted to sub-Tenon during the surgery because of intolerable pain. CONCLUSIONS: Whereas lidocaine supported xylocaine jelly anesthesia provided acceptable analgesia for 90% of patients operated, sub-Tenon anesthesia proved to deliver better intraoperative comfort in all patients receiving sclerocorneal incision cataract surgery.

[Massive subretinal hemorrhages. A challenge for vitreous body surgeons]. / Die subretinale Massenblutung. Eine Herausforderung für den Glaskörperchirurgen.

BACKGROUND: In patients with advanced age-related macular degeneration (AMD), massive subretinal hemorrhage may sometimes be the reason for a loss of peripheral vision, leading to a significantly reduced quality of life. PATIENTS AND METHODS: During the years 1995-2001 we operated five eyes (five consecutive patients) with acute massive subretinal hemorrhage extending into all four quadrants and profoundly reduced vision in the fellow eye due to a Junius-Kuhnt macular scar. Within an interval of 1-2 weeks after the bleeding, pars plana vitrectomy with peripheral retinotomy was performed. After the retina was turned upside down and the partially liquified blood was removed, the underlying subfoveal CNV membrane was removed with a vitrectome. Three phakic eyes required additional cataract surgery and IOL implantation. The retina reattached under PFCL and a silicone oil tamponade applied for 3-6 months. RESULTS: The removal of the subretinal hemorrhage was without complications. The size of the subretinal membrane was between 4 and 6 PD with partially fibrovascular tissue. After the membrane was removed, a large central pigment epithelium defect made a macular rotation impossible. Visual acuity of hand motion improved from preoperatively 0.05 to postoperatively 1/35 to 0.1 after a follow-up of 3-6 months. CONCLUSION: In patients with such an extremely reduced visual acuity and visual field, subretinal surgery with removal of the subretinal blood may achieve sufficient vision for the patients' orientation.

[Measurement of scotopic pupils: comparison of scotic pupil measurements using a colvard pupilometer and the slitlamp green light test]. / Vermessung der skotopischen PupilleEin Vergleich zwischen dem Pupillometer nach Colvard und der Spaltlampenmessung mit dem grünen Licht.

PURPOSE: The aim of the study was to compare the accuracy and the reproducibility of scotopic pupil measurements using two different methods. PATIENTS AND METHODS: We developed a simple test to measure scotopic pupil diameters using a narrow slit of light through a green filter of the Haag-Streit slitlamp. A total of 100 eyes from 50 refractive surgery candidates were prospectively examined by 2 independent investigators using both the Colvard pupilometer (Oasis/USA) and Sekundo's slitlamp green light test. Results were compared using all pairwise multiple comparison procedures (Student-Newman-Keuls method, SigmaStat/Jandel Scientific). The mean age of the patients was 36.3 years with a male:female ratio of 16:34. The colour of the iris was considered blue for 36 individuals and brown for the remainder. RESULTS: Reproducibility: the right eye mean pupil diameter using Sekundo's method was 6.4 mm (+/-0.9) measured by both the first (Slit 1R) and the second (Slit 2R) investigator. The left eye mean pupil diameter was 6.5 mm (+/-1) (Slit 1L) and 6.35 mm (+/-1) (Slit 2L), respectively. The following measurements were obtained with the Colvard pupillometer: (Colv1R)=6.25+/-0.85 mm, (Colv2R)=5.99+/-1 mm, (Colv1L)=6.15+/-0.91 mm, (Colv2L)=6.05+/-0.9 mm. There were no statistically significant differences between the two investigators within the same method of examination. Comparability:The data of both investigators were combined to form 4 groups: (Slit R)=6.4+/-0.96 mm, (Slit L)=6.4+/-1 mm, (Colv R)=6.05+/-0.9 mm, (Colv L)=6.1+/-0.93 mm. There was a significant difference ( p=0.024) between the two methods for both right and left eyes. Particularly for large pupils, the slitlamp green light measurements were significantly higher (up to 0.35 mm) than those with Colvard's device. CONCLUSIONS: The slitlamp green light test provides similar reproducibility for the measurement of the scotopic pupil diameter as the commercially available Colvard pupilometer.

Primary vitrectomy in complicated rhegmatogenous retinal detachment--a survey of 205 eyes.

INTRODUCTION: In a few types of rhegmatogenous retinal detachment (RRD), scleral buckling (SB) has a lower success, and, here, pars plana vitrectomy (PPV) is a good alternative option. This survey reviews the indications and the surgical outcome of primary PPV with internal tamponade. PATIENTS AND METHODS: We reviewed 205 eyes operated by primary PPV for RRD at the Department of Ophthalmology of the Philipps University Marburg between the years 1990 and 1997. The indications of PPV were: holes greater than 90 degrees; holes posterior to the equator; proliferative vitreoretinopathy grade C; pseudophakic status. RESULTS: A complete reattachment of the retina after absorption of the gas or after silicone oil removal was achieved by 1 operation in 146 eyes (71.2%) and in 195 eyes (95.2%) by a second intervention. CONCLUSION: Although SB is the standard procedure for the treatment of RRD, complicated cases can be treated successfully with primary PPV.