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Recent studies deciphering the transcriptional profile of choroidal neovascularization (CNV) in body donor eyes with neovascular age-related macular degeneration are limited by the time span from death to preservation and the associated 5′-RNA degradation. This study therefore used CNV and control specimens that were formalin-fixed and paraffin-embedded immediately after surgical extraction and analyzed them by a 3′-RNA sequencing approach. Transcriptome profiles were analyzed to estimate content of immune and stromal cells and to define disease-associated gene signatures by using statistical and bioinformatics methods. This study identified 158 differentially expressed genes (DEGs) that were significantly increased in CNV compared with control tissue. Cell type enrichment analysis revealed a diverse cellular landscape with an enrichment of endothelial cells, macrophages, T cells, and natural killer T cells in the CNV. Gene ontology enrichment analysis found that DEGs contributed to blood vessel development, extracellular structure organization, response to wounding, and several immune-related terms. The S100 calcium-binding proteins A8 (S100A8) and A9 (S100A9) emerged among the top DEGs, as confirmed by immunohistochemistry on CNV tissue and protein analysis of vitreous samples. This study provides a high-resolution RNA-sequencing–based transcriptional signature of human CNV, characterizes its compositional pattern of immune and stromal cells, and reveals S100A8/A9 to be a novel biomarker and promising target for therapeutics and diagnostics directed at age-related macular degeneration.

The newly started use of atorvastatin eliminated the need for further intravitreal injections of ranibizumab for 37 months in a case of wet form of age related macular degeneration(AMD). Repeated optical coher ence tomographic examinations documented the absence of intra - or subretinal fluid. The known effects of statins on endothelial function might also improve retinal capillary endothelial function and reduce or eliminate fluid leakage into the intra - or subr etinal space. This would intervene earlier in one important disease mechanism of AMD than the injection of anti - VEGF therapies. A randomized study is necessary to prove this hypothesis.

Beschrieben wird der Fall eines 49-jahrigen Patienten mit inkomplettem Vogt-Koyanagi-Harada-Syndrom. Anamnestisch bestanden seit 2 Wochen intermittierende wechselseitige Visusbeschwerden. Der beste korrigierte Visus betrug beidseits 0,1. Neben einer anterioren Uveitis rechts fielen funduskopisch an beiden Fundi multiple blasige Netzhautveranderungen auf. In der optischen Koharenztomographie (SD-OCT) bestatigte sich das funduskopische Bild als multiple intraretinale Zysten und Areale mit neurosensorischer Abhebung. Unter topischer und systemischer Steroidtherapie kam es zu einer raschen Reduktion der intraretinalen Zysten und der neurosensorischen Abhebung. Der Ruckgang in der SD-OCT korrespondierte mit einer entsprechenden Visusverbesserung.

Retinal vein occlusion (RVO) is one of the most frequently occurring retinal vascular disorders. Occlusion of either the central retinal vein or one of its branches leads to disruption of retinal blood flow and subsequent tissue hypoxia. The disease mechanisms underlying RVO are not fully understood. One seminal study by Green et al1 has found venous thrombi in postmortem eyes of patients with RVO. However, it is not fully established whether thrombus formation is the cause or rather a consequence of RVO. The main presenting symptom in patients with RVO is painless vision loss that usually develops over the course of hours to days. The vision loss perceived by patients with RVO is partially the result of central macular edema (CME) that develops secondary to the venous occlusion. Central macular edema is thought to result from a combination of increased intraluminal pressure in occluded veins and increased amounts of the permeability factor vascular endothelial growth factor (VEGF) that is expressed as a result of tissue hypoxia in retinas with impeded circulation.2 The extent to which CME affects visual acuity in patients with RVO is illustrated by numerous studies reporting a decline in CME with a concomitant rise in visual acuity after intravitreal injection of anti-VEGF antibodies.3–12 Inversely, visual acuity often deteriorates during phases of CME rebound, when intravitreal VEGF inhibition ceases to sufficiently block VEGF signaling.13 Vascular endothelial growth factor expression is known to be regulated through the hypoxia-sensitive transcription factor Hif1α.14 Erythropoietin (EPO) is similarly induced by Hif1α in a hypoxia-dependent fashion.15 In addition to its well-established hematopoietic effects, EPO has neuroprotective properties both in the retina16 and in models of ischemic brain injury17 in which EPO has been shown to limit the extent of secondary brain edema.18 With regard to retinal EPO expression in patients with RVO, the data published to date are still fragmentary. One study by Inomata et al19 found a significant 12-fold EPO increase in the vitreous of 12 patients with branch RVO. Another study by Garci-Arumi et al20 reported a fourfold increase in vitreal EPO in a cohort of nine patients with central RVO and three patients with branch RVO. However, this increase was not statistically significant. The aim of our study was to measure vitreal EPO in patients with RVO and control subjects without vascular disease and to identify parameters that correlate with vitreal EPO concentrations and could thus account for the reported differences.

Central retinal artery occlusion (CRAO) is an ophthalmological emergency situation. Known risk factors are arterial hypertension, cardial arrhythmia, arteriosclerosis, hypercholesterolemia and diabetes. Elderly patients should be examined for an arteritic genesis. Young patients (< 45 years) without typical risk factors may suffer from thrombophilia. There is no uniform recommendation on how to treat non-arteritic CRAO. Many different interventions have been suggested in the literature, i. e., massaging the eye, systemic or local reduction of intraocular pressure, anticoagulation, either systemically administered venous thrombolysis or supraselective intra-arterial thrombolysis. In this review we present the causes of CRAO and diagnostic means to detect causes; we also critically discuss previously described therapeutic options. It is our aim to provide a guide through the necessary interdisciplinary diagnostics in co-operation with internal medicine and neurology and to recommend a multimodal therapy in patients with non-arteritic CRAO.

The novel therapeutic principle of intravitreal drug therapy for retinal vein occlusion has become an integrated constituent of clinical practice over the last years. The two substance classes that have been evaluated in large randomised clinical trials so far are corticosteroids and inhibitors of vascular endothelial growth factor (VEGF). The reported treatment success of these intravitreally administered substances has lead not only to a paradigm shift in clinical care but has also advanced our understanding of the underlying pathophysiological principles of retinal vein occlusions. In this review the different substances are discussed, their mechanisms of action are analysed and the results of the large clinical trials available to date are critically evaluated. Furthermore, an approach to integrate these novel treatment options into the exisitng treatment regimes for retinal vein occlusions is suggested.

OBJECTIVE The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center. RESEARCH DESIGN AND METHODS This was a 12-month, multicenter, sham-controlled, double-masked study with eyes (age >18 years, type 1 or 2 diabetes, central retinal thickness [CRT] ≥300 μm, and best corrected visual acuity [BCVA] of 73–39 ETDRS letters [Early Treatment Diabetic Retinopathy Study]) randomly assigned to intravitreal ranibizumab (0.3 or 0.5 mg; n = 51 each) or sham (n = 49). The treatment schedule comprised three monthly injections, after which treatment could be stopped/reinitiated with an opportunity for rescue laser photocoagulation (protocol-defined criteria). After month 1, dose-doubling was permitted (protocol-defined criteria, injection volume increased from 0.05 to 0.1 ml and remained at 0.1 ml thereafter). Efficacy (BCVA and CRT) and safety were compared between pooled ranibizumab and sham arms using the full analysis set (n = 151, patients receiving ≥1 injection). RESULTS At month 12, mean ± SD BCVA improved from baseline by 10.3 ± 9.1 letters with ranibizumab and declined by 1.4 ± 14.2 letters with sham (P < 0.0001). Mean CRT reduction was 194.2 ± 135.1 μm with ranibizumab and 48.4 ± 153.4 μm with sham (P < 0.0001). Gain of ≥10 letters BCVA from baseline occurred in 60.8% of ranibizumab and 18.4% of sham eyes (P < 0.0001). Safety data were consistent with previous studies of intravitreal ranibizumab. CONCLUSIONS Ranibizumab is effective in improving BCVA and is well tolerated in DME. Future clinical trials are required to confirm its long-term efficacy and safety.

Purpose Bevacizumab (Avastin®) was first used clinically in 2005. Reports on the treatment of more than 600 patients with central retinal vein occlusion (CRVO) have been published to date. However, there are limited data on the long-term effects of bevacizumab in patients with CRVO. Methods We retrospectively re-evaluated 10 patients with CRVO who were initially part of one of the first published case series on the short-term effects of bevacizumab (1). The patients were invited for a follow-up visit 2 years after their initial bevacizumab injection. Study endpoints were changes in visual acuity (VA) and central macular edema (CME) compared to 1) baseline values and 2) short-term values after the initial injection. Results Short-term VA gain had been 2.9 lines 3 weeks after the first bevacizumab injection. Two years later, mean VA gain vs baseline was 1.6 lines. Low baseline VA and good response to the first injection correlated positively with higher long-term VA gains (Pearson correlation of r = 0.50 and r = 0.66). There was no correlation for injection number, occlusion time, or CME changes with long-term VA gain. Conclusions The initial short-term VA gain after bevacizumab treatment was not always maintained over a 2-year period despite repeated injections. Patients with low baseline VA and good response to the first injection seemed to benefit most from repeated bevacizumab injections.

Die arteriovenose Dissektion (AVD) ist ein chirurgisches Verfahren, um beim retinalen Venenastverschluss Arterie und Vene im Bereich der Kreuzungsstelle zu trennen und damit eine Ursache des Verschlusses zu beseitigen. Da bisher nur Studien der Evidenzebene 3 publiziert wurden, ist der tatsachliche Wert der AVD zurzeit noch nicht abschliesend zu beurteilen. Wir halten diesen Eingriff bei geeigneter Kreuzungsstelle fur vertretbar, wenn der Verschluss nicht alter als 3 Monate ist und die Sehscharfe ≤0,4 betragt.

Originating from therapeutic concepts in oncology, angioinhibitory strategies have changed the way ophthalmological patients are treated for a variety of diseases like age-related macular degeneration, diabetic retinopathy or retinal vein occlusion. It is likely that these therapeutic options will not be limited to retinal disease, but will also prove useful for corneal disorders associated with lymph- or angiogenesis. This review is intended to provide a concise overview of the current options investigated in clinical trials.

For many decades, conventional buckling surgery has been the gold standard for treating rhegmatogenous retinal detachment. The surgical technique has not changed markedly during this period; the three main buckling techniques currently used are the radial sponge, segmental sponge, and encircling band. With one of these options, an anatomic success rate of over 90% can be achieved in "simple" forms of retinal detachment. In pseudophakic eyes, however, the primary reattachment rate after buckling procedures is lower. Pneumatic retinopexy, because of its lower success rate, has not found general acceptance in Europe and is used only in selected cases. Concerning the results of the SPR study, many vitreoretinal surgeons were surprised that in the subgroup of phakic eyes, scleral buckling surgery achieved a comparable reattachment rate and better functional results even in this group of patients with complex hole configuration. This gives physicians reason to critically question the current trend of primary vitrectomy even in eyes with uncomplicated preoperative pathology and to reassess scleral buckling surgery. The longer learning curve to perform buckling surgery should be accepted. Because successful repair depends on careful preoperative examination, thorough training in binocular ophthalmoscopy skills with scleral depression should remain an essential part of the surgeon's education.

Purpose: Endogenous endophthalmitis is a severe and potentially blinding complication caused by haematogenous spreading of microorganisms. We evaluated the causative microorganisms, disposition to and prognosis of the disease. Methods: Thirty-one eyes of 28 patients were treated between 1996 and 2006 as the result of an endogenous endophthalmitis. Results: The microorganisms responsible for infection could be identified in 94% of all eyes investigated. Candida isolates were obtained in 15, gram-positive isolates in 11, gram-negative in one and Aspergillus in two of the 29 eyes studied. The majority of patients suffered from severe general disease (immuno-deficiency, severe surgical procedures, diabetes mellitus) and one third were intravenous drug abusers. Only one patient was otherwise healthy. The prognosis depended on the causative microorganisms. Whereas none of the eyes with Candida infection became blind, all except two of the eyes with gram-positive bacteria, Nocardia or Aspergillus infection lost visual function or had to be enucleated. Conclusion: Compared to postoperative endophthalmitis, patients with endogenous endophthalmitis are more likely to have Candida isolates. Visual prognosis depends mainly on the underlying microorganisms, and is particularly poor in the case of infection with gram-positive bacteria or Aspergillus.

Das funduskopisch sichtbare zystoide Makulaodem nach unkomplizierter Kataraktoperation (PZMO) tritt in 1–3% der Falle auf. Es hat eine gute Prognose. Nur 10% der Odeme persistieren uber 2 Jahre hinaus. Die prophylaktische Behandlung von Augen ohne Begleiterkrankungen mit nichtsteroidalen Antiphlogistika (NSAD) und Steroiden hat keinen Einfluss auf den Endvisus. Unter bestimmten Voraussetzungen scheint sie jedoch sinnvoll. Es werden Risikofaktoren besprochen, die das Entstehen eines PZMO begunstigen. Der Verlauf des akuten und chronischen PZMO ist zwar medikamentos beeinflussbar – insgesamt ist die Studienlage, was die Behandlung dieses haufigen Problems angeht, jedoch schlecht. In diesem Zusammenhang mochten wir das Freiburger Therapieschema zum PZMO vorstellen.

The range of therapeutic options for the treatment of retinal vein occlusions has been decisively extended by three new surgical methods: radial optic neurotomy (RON) and retinal endovascular lysis (REVL) for central retinal vein occlusion, and arteriovenous dissection (AVD/sheathotomy) for branch retinal vein occlusion. None of those methods has been tested in randomised studies meeting the requirements of evidence-based medicine. It is therefore difficult to assess the relative values of the individual procedures and determine in what precise circumstances each is indicated. The difficulties are compounded further by the use of these techniques in association with new and promising intravitreally injected drugs (e.g. steroids and angioinhibitors), which makes it even more difficult to assess the real efficacy of the surgical methods. In this paper we discuss the three different surgical methods and try to evaluate their clinical benefit.

To evaluate the potential role of radial optic neurotomy (RON), a new surgical technique has been recently proposed for treating central retinal vein occlusion (CRVO). It is hypothesized that CRVO constitutes a neurovascular compartment syndrome at the site of the lamina cribrosa, which can be alleviated by performing a radial incision at the nasal part of the optic nerve head, relaxing the cribriform plate and the adjacent sclera. One hundred and seven patients were treated with RON for CRVO at five collaborating ophthalmologic centers. All patients were evaluated by a standardized protocol. For analysis of the angiographic and fundus findings, reference images were used. Intraoperative and postoperative complications were reviewed. On 55 right and 52 left eyes of 107 patients (55.6% male, 44.4% female) with a median age of 68 years (range 21–91 years), RON was performed. The median follow-up time was 6 months (range 1–24 months). The median preoperative visual acuity (VA) was 0.05 (logMAR 1.3), increasing to a median postoperative VA of 0.08 (logMAR 1.1). Patients with an interval of more than 90 days between RON and onset of CRVO showed no significant change in VA at the 6-month follow-up. Severe peripapillary swelling of the optic nerve head prior to RON resulted in an average increase of 4.2 lines in VA at the 6-month follow-up. Angiographic findings of shunt vessels were seen in 18/30 cases after 12 months and were accompanied by an average improvement of VA of six lines. Visual field tests showed various defects in 86.8% of all cases. In one patient an iatrogenic injury of the central retinal artery occurred (0.9%). Despite the potential risk of visual field defects, RON seems to be a quite safe procedure. The majority of patients showed rapid normalization of the morphologic fundus findings, with an improvement in VA uncommon for the natural history of CRVO. No significant change in VA was seen in patients with an interval of more than 90 days between the onset of CRVO and RON. A prospective study is warranted for further investigation.

Intravitreal application of triamcinolone acetonide has become increasingly popular for the treatment of various retinal disorders. However, dosage, mode of preparation and application differ worldwide. The aim of this study was to find a safe vehicle that would allow intravitreal injection of an exact amount of triamcinolone acetonide without potentially retinotoxic preservatives.Solutions of triamcinolone acetonide with a theoretical concentration of 4 mg/0.2 ml were prepared following one sedimentation (A) and two filtration (B, C) methods. In addition, a filtration method using carboxymethylcellulose 2% as a carrier (D) was established. During processing and after injection into an eye model, the crystals were quantified by weight and high-performance liquid chromatography (HPLC), and, hence, the rate of crystal loss during this process was determined.The initial preparation contained 93-106% of the calculated quantity. Method A, containing the entire vehicle, delivered 45%+/-7.3% of the target quantity to the eye model, whereas the vehicle-free methods B and C delivered 15%+/-6.9% and 11%+/-3.2%, respectively. Using carboxymethylcellulose 2% as a preservative-free vehicle, we found 93%+/-3.7% of the calculated amount in the eye model. The missing crystals were mainly sticking to the walls of the syringes and needles used for transfer.Common methods for preparing triamcinolone acetonide vary in the amount of drug actually injected intravitreally. Carboxymethylcellulose is an ideal carrier substance for intravitreal application of an exact dose of triamcinolone acetonide without preservatives.

Arteriovenous dissection (sheathotomy) is a new therapeutic option in patients with branch retinal vein occlusion (BRVO) and macular involvement. We present an angiographic follow-up of 22 patients who underwent arteriovenous dissection (AVD).Twenty-two patients (15 women; mean age 68.7+/-8.0 years) were examined preoperatively and 6 weeks, 3 months, 6 months, and 1 year after AVD. For assessment of retinal hemodynamics, arteriovenous passage time (AVP) of the affected and unaffected branches at first (AVPe) and at maximal (AVPmax) venous filling were measured. Changes in the foveal avascular zone (FAZ) were calculated to determine foveal structural changes. Visual acuity was assessed as functional parameter.The early AVP (AVPe) of the affected branch increased from 4.4+/-0.8 s preoperatively to 4.9+/-0.6 s 6 weeks after surgery and decreased to 2.7+/-0.4 s 1 year after surgery (p=0.05). When compared to the unaffected control branch, AVPe was significantly increased in the affected branch preoperatively (4.5+/-0.8 s versus 1.5+/-0.2 s, p0.01), 6 weeks (4.9+/-0.6 s versus 2.1+/-0.3 s, p0.01), 3 months (2.7+/-0.4 s versus 1.5+/-0.2 s, p0.01), and 6 months (3.1+/-0.4 s versus 2.2+/-0.3 s, p=0.02) after AVD. After 1 year, AVPe no longer differed between the affected and the control branch (2.7+/-0.4 s versus 2.6+/- 0.3 s). AVPmax was significantly increased in the affected branch preoperatively (11.8+/-0.8 s versus 7.7+/-1.0 s, p0.05). The AVPmax in the affected branch with the exception of 3 months after surgery (10.2+/-1.1 s, p0.01) was no longer elevated when compared to preoperative values. The area of the FAZ did not change significantly but showed a trend for enlargement.AVD for decompression of BRVO leads to a significant decrease of AVP and may ameliorate retinal perfusion in the affected branch.

JC virus (JCV) is a human polyomavirus that exists in at least eight different genotypes as a result of coevolution with different human populations all over the world. Well adapted to its host, it usually persists in the kidneys and possibly the brain. If the host becomes immunodeficient, JCV can cause the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). There is increasing evidence that JCV is transactivated by cytomegalovirus (CMV) and the human immunodeficiency virus (HIV). Both CMV and HIV can infect the retina of acquired immunodeficiency syndrome (AIDS) patients, causing severe necrosis in the case of CMV retinitis or a mild HIV-associated vasculopathy, with bleeding and cotton wool spots. The authors therefore investigated by polymerase chain reaction (PCR) whether DNA of these three viruses was detectable in paraffin-embedded eyes of AIDS patients with a clinical history of CMV retinitis. From a total of 65 eyes, JCV was detected in 21 (32%). Thirty-six (55%) were positive for CMV and 6 (9%) for proviral DNA of HIV. JCV and CMV were found in 13 eyes, JCV and HIV in 3 eyes, CMV and HIV in 1 eye, and DNA from all three viruses in 1 eye. The JCV genotypes were types 1A, 2A, 2E, 3, and 4. In 21 eyes of patients without AIDS, only one sample was JCV positive. In conclusion, JCV DNA can be detected in ocular tissue of AIDS patients at a significantly higher level than in eyes of nonimmunosuppressed patients. Further investigations will help to decide if JCV contributes to the retinopathy caused by CMV and HIV.

In this review ophthalmological diseases caused by herpes simplex virus, varicella zoster virus, Epstein-Barr virus, cytomegaly virus or adenovirus are described briefly. The main therapeutic options are discussed placingemphasis especially on prospective randomised trials.

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.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.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.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.

BACKGROUND: Central retinal vein occlusion (CRVO) is a common disease characterized by a disrupted retinal blood supply and a high risk of subsequent vision loss due to retinal edema and neovascular disease. This study was designed to assess the concentrations of selected signaling proteins in the vitreous and blood of patients with ischemic CRVO. METHODS: Vitreous and blood samples were collected from patients undergoing surgery for ischemic CRVO (radial optic neurotomy (RON), n = 13), epiretinal gliosis or macular hole (control group, n = 13). Concentrations of 40 different proteins were determined by an ELISA-type antibody microarray. RESULTS: Expression of proteins enriched in the vitreous (CCL2, IGFBP2, MMP10, HGF, TNFRSF11B (OPG)) was localized by immunohistochemistry in eyes of patients with severe ischemic CRVO followed by secondary glaucoma. Vitreal expression levels were higher in CRVO patients than in the control group (CRVO / control; p < 0.05) for ADIPOQ (13.6), ANGPT2 (20.5), CCL2 (MCP1) (3.2), HGF (4.7), IFNG (13.9), IGFBP1 (14.7), IGFBP2 (1.8), IGFBP3 (4.1), IGFBP4 (1.7), IL6 (10.8), LEP (3.4), MMP3 (4.3), MMP9 (3.6), MMP10 (5.4), PPBP (CXCL7 or NAP2) (11.8), TIMP4 (3.8), and VEGFA (85.3). In CRVO patients, vitreal levels of CCL2 (4.2), HGF (23.3), IGFBP2 (1.23), MMP10 (2.47), TNFRSF11B (2.96), and VEGFA (29.2) were higher than the blood levels (vitreous / blood, p < 0.05). Expression of CCL2, IGFBP2, MMP10, HGF, and TNFRSF11B was preferentially localized to the retina and the retinal pigment epithelium (RPE). CONCLUSION: Proteins related to hypoxia, angiogenesis, and inflammation were significantly elevated in the vitreous of CRVO patients. Moreover, some markers known to indicate atherosclerosis may be related to a basic vascular disease underlying RVO. This would imply that local therapeutic targeting might not be sufficient for a long term therapy in a systemic disease but hypothetically reduce local changes as an initial therapeutic approach. peerReviewed

Background Optic neuropathy has been reported to occur during antiarrhythmic therapy with amiodarone. Whether or not there is a causal relationship has been discussed controversely. Patients Three patients presented with a visual impairment three to seven months after starting amiodarone therapy. In all three patients both optic discs were swollen and showed hemorrhages on the margin. After discontinuing amiodarone, the vision improved and the swelling of the optic discs resolved. Conclusion The bilateral occurrence at the same time, the close time correlation with the amiodarone application and the improvement after discontinuing amiodarone suggest that our three patients suffered from a toxic effect of amiodarone rather than an incidental other disease, as for instance ischemic optic neuropathy.

· Background: To correlate the retinal ganglion cell pattern to visual acuity and visual field data in a patient with bilateral optic disc drusen, a quantitative clinicopathological study was carried out. · Methods: Both retinae of a patient with optic drusen were whole-mounted. Retinal ganglion cell counts were made using a sampling scheme covering the whole retina and compared to the findings in 10 normal retinae. Relative ganglion cell reduction in the drusen retinae was correlated to clinical data. · Results: The total retinal ganglion cell count was reduced from 1244858±98736 in normal retinae to 305319 on the right and 527571 on the left eye with optic disc drusen. Large ganglion cells had a better chance of survival. Parafoveal ganglion cell loss was 57% for the right and 36% for the left eye, while visual acuity was 0.8 and 1.0 respectively. The mean light sensitivity loss increased from the centre (6.2 dB) to paracentral (9.9 dB), mid-peripheral (13.7 dB) and outer peripheral (15.0 dB) retina, while ganglion cell losses were smallest in outer peripheral retina (21.9%), followed by central (53.0%), mid-peripheral (70.9%) and paracentral retina (87.7%). · Conclusion: These data validate Frisen’s theory on central retinal resolution and provide the structural basis for the clinical rule that low visual acuity should not be attributed to disc drusen. Automated light sense perimetry gives an inadequate picture of retinal damage caused by optic disc drusen.

BACKGROUND: The shaken baby syndrome is a form of child abuse in young children. Typical are intracranial and intraocular bleedings. As external injuries are often missing, the shaken baby syndrome may easily be overlooked. Intraocular bleeding is a major diagnostic sign and can prove the diagnosis, if child abuse is suspected by the paediatrician. Thus critical family situations can be uncovered and long term help can be initiated. PATIENTS: Between 1991 and 1997 seven babies (age two to nine months) with intraocular bleedings were examined. Diagnosis, differential diagnosis and prognosis of the shaken baby syndrome are presented with these children. RESULTS: In two of the seven children a non-accidental trauma and shaken baby syndrome was obvious. In three cases the diagnosis of a shaken baby syndrome was most probable. In one child intraocular bleeding was possibly caused by a fall three months earlier. One child had retinal bleedings after resuscitation. In two cases a vitrectomy was performed. The follow up was two months to six years. In two children intraocular bleeding resolved completely, three children developed mild to severe amblyopia and two children became blind. Vitrectomy could not prevent loss of sight. CONCLUSIONS: Sudden cerebral symptoms or intraocular bleedings in otherwise healthy young children are suspicious for child abuse. A shaken baby syndrome has to be considered. Thus funduscopic examination in mydriasis is obligatory. The prognosis depends on the severeness of ocular hemorrhages and cerebral lesions. Language: de

Purpose: There is considerable overlap in the clinical profile of patients with idiopathic optic neuritis(ON) and anterior ischemic optic neuropathy (AION). We tested the hypothesis that the retrobulbar diameter of the optic nerve may be a criterion for the differential diagnosis between ON and AION. Methods: The diameter of the optic nerve was measured by B-scan ultrasonography with the eye in an abducted position. Only patients with a unilateral optic neuropathy were included, 16 ON patients (mean age 24years, 5 with and 11 without disc swelling) and 9patients with AION (mean age 72 years). As controls for the ON patients 10 young normal subjects (mean age25 years) and as controls for the AION patients 10elderly subjects with eye problems not related to the optic nerve (mean age 76 years) were examined. Results: In the ON patients with disc swelling the diameter of the optic nerve was 5.4 ± 0.5 mm in the affected and 3.0 ± 0.3 mm in the unaffected side. This difference was significant (Wilcoxon-test, p = 0.043). In the ON patients without disc swelling the diameter of the optic nerve was 4.4 ± 0.4 mm in the affected and 3.0 ± 0.3 mm in the unaffected side. This difference was significant (Wilcoxon-test, p = 0.003). In the AION patients the diameter of the optic nerve was 3.0 ± 0.3 mm on the affected and2.8 ± 0.4 mm on the unaffected side. This difference was not significant (Wilcoxon-test, p =0.093). Comparing the optic nerves with ON and AION to those of the controls, the diameter was significantly enlarged in the nerves with ON and normal in the nerves with AION (one factor repeated ANOVA). Conclusion: The diameter of the optic nerve is increased in ON without disc swelling and even more so in ON with disc swelling. The enlargement is probably due to edema of the nerve itself, not the surrounding subarachnoidal space. In AION, the diameter of the optic nerve is normal. Measuring the diameter of the optic nerve by B-scan ultrasonography is particularly useful in the differential diagnosis between ON with disc swelling and AION.

Radial optic neurotomy is a novel therapy for the treatment of ischemic central retinal vein occlusion. To date, the visual results are encouraging. Cutting in the optic nerve can cause visual field defects as shown in the presented case. This complication will reduce the value of this new surgical procedure and should be weighed against still unsettled advantages.

Background To reduce the burden of frequent visits at the physician we have checked (I) for which ocular manifestations in HIV-infection screening of asymptomatic patients is worthwhile and (II) which parameters may indicate patients at risk for CMV-retinitis. Patients and Methods The clinical data of 215 HIV-infected patients were analyzed retrospectively. Only those ocular manifestations were considered suitable for screening that (a) endanger vision, (b) are treatable, (c) can be diagnosed sufficiently early and (d) are common. Furthermore (1) CDC-stage, (2) CD4+ count, (3) HIV-retinopathy, (4) CMV-uria and (5) CMV-antibodies were checked for their usefulness in indicating patients at risk for CMV-retinitis. Results Ophthalmological screening of asymptomatic HIV-patients should focus on cytomegalovirus (CMV)-retinitis because early diagnosis of this common blinding disease improves the visual outcome. 85 of 215 HIV-infected patients had a CD4+ count less than 50 cells/μl. 25% of these patients developed CMV-retinitis (21/85). The risk for CMV-retinitis rose to 38% (13/34) when the low CD4+ count was accompanied by CMV-uria. The proportion of patients with CMV-retinitis did not increase when HIV-retinopathy had been diagnosed earlier (12/48=25%). CMV-serology and CDC-classification were not helpful in screening for CMV-retinitis. Conclusions We recommend the following ophthalmological screening scheme for HIV-patients without ocular symptoms: (1) patients with a CD4+ count

Background The incidence of motility disturbances induced by episkeletal buckle operations for retinal detachment has been reported to range between 7 and 77%. We anticipated a relation between the buckle size and the incidence and extent of motility disturbances. Patients and methods We examined 45 patients 2 to 4 years after successful retinal detachment surgery with a radial buckle. The buckle diameter was 3-11 mm. Patients were examined for diplopia and heterophoria in the primary position and in 20° secondary and tertiary gaze deviations. Stereopsis was determined using the TNO plates. Refractive error and visual acuity were also measured. Results Heterophoria measurements in the various of gaze revealed a hypermotility in 22/45 cases. A hypomotility was encountered only in one of the 45 cases. In 40 of the 45 cases the field of binocular single vision had a radius of at least 20°. 39 of the 45 patients had stereopsis (after macular detachment 17/22, without macular detachment 22/23). 7/32 patients with a buckle of ≥5 mm reported on diplopia, but none of the 13 patients with a buckle of ≤4 mm. Heterotropia in the primary position was found in one of the 45 cases. He had three buckles, a 10.5 mm buckle under the superior rectus muscle of one eye and a 4 and 7.5 mm buckle under the inferior oblique and rectus muscles of the other eye. The resulting vertical deviation was succesfully treated with prisms. Motility disturbances in the upper field of gaze were found in 2 of 45 cases with buckles of 5 and 7.5 mm. Diplopia was not permanent in these cases. Discussion Hypermotility towards the position of the buckle may be explained by a deviation of the adjacent rectus muscles, after sharp preparation and shrinkage of the intermuscular septum. Conclusion Since motility disturbance were encountered only with buckles of ≥5 mm, small buckles (≤4 mm) should be applied whenever possible.

BACKGROUND In patients with non-arteritic anterior ischaemic optic neuropathy disc parameters have been measured with a largely objective method (Optic Nerve Head Analyzer). We wanted to find out, whether the measurements of different disc parameters allow an assertion of predisposition to AION. METHODS Measurements have been done with the Optic Nerve Head Analyzer (ONHA). In 25 patients with AION disc area and neuroretinal rim area was measured in the nonaffected fellow eye. The results were compared to those of 19 healthy subjects. In 12 of the 25 patients the disc structure of the AION-eye was measured over time with an average of 4 measurements in 16 months. RESULTS 1) Disc area and neuroretinal rim area of the AION-eyes do not differ significantly from those of the healthy subjects. 2) Disc area and neuroretinal rim area of the healthy fellow eyes of the AION patients were not significantly different from those of the healthy subjects. 3) Measurements of disc parameters over time did not show significant differences between the parameters of the beginning of AION and after 16 months. CONCLUSIONS Measurements of disc area and neuroretinal rim area with the Optic Nerve Head Analyzer do not allow assertions of predisposition to AION.

Purpose Precise monitoring of active angiogenesis in neovascular eye diseases such as age-related macular degeneration (AMD) enables sensitive use of antiangiogenic drugs and reduces adverse side effects. So far, no in vivo imaging methods are available to specifically label active angiogenesis. Here, we report such a technique using fluorophore-labeled cationic liposomes (CL) detected with a standard clinical in vivo scanning laser ophthalmoscope (SLO). Methods C57Bl/6 mice underwent laser coagulations at day 0 (d0) to induce choroidal neovascularization (CNV). Liposomes labeled with Oregon green, rhodamine (Rh), or indocyanine green (ICG) were injected into the tail vein at various time points after laser coagulation, and their fluorescence was observed in vivo 60 min later using an SLO, or afterwards in choroidal flatmounts or cryosections. Results SLO detected accumulated fluorescence only in active CNV lesions with insignificant background noise. The best signal was obtained with CL-ICG. Choroidal flatmounts and cryosections of the eye confirmed the location of retained CL in CNV lesions. Neutral liposomes, in contrast, showed no accumulation. Conclusions These results establish fluorophore-labeled CL as high affinity markers to selectively stain active CNV. This novel, non-invasive SLO imaging technique could improve risk assessment and indication for current intraocular antiangiogenic drugs in neovascular eye diseases, as well as monitor therapeutic outcomes. Labeling of angiogenic vessels using CL can be of interest not only for functional imaging in ophthalmology but also for other conditions where localization of active angiogenesis is desirable.

This case study explores the histopathological findings 9 months after retinal endovascular lysis (REVL) in a 62-year-old woman having a 7-week-old, highly ischaemic central retinal vein occlusion (CRVO) with hand movement vision. Angiographic examination 3 days postoperatively did not show improved arteriovenous passage time. In addition, the patient’s postoperative vision did not change, and despite intensive photocoagulation and cryotherapy in the early postoperative period, the globe had to be removed 9 months later because of painful phthisis. Histological findings at the site of puncture were epiretinal membrane, interrupted internal limiting membrane and thickened venous wall. This is the first case to show the histological changes after surgical REVL in a human eye. In this case, REVL did not prevent neovascular glaucoma despite successful recombinant tissue plasminogen activator (rt-PA) injection in a venous branch close to the papilla. It was concluded that rt-PA injection after 7 weeks of CRVO is too late.

AIM--Aim of the study was investigation of the effect of isovolemic hemodilution in patients younger than 50 years on the course of central retinal vein occlusion (CRVO) and to compare these results with those of older patients with CRVO. PATIENTS AND METHODS--We performed a prospective study on 35 patients younger than 50 years who were suffering from a central retinal vein occlusion. These patients were all treated by isovolemic hemodilution and compared to a group of older patients with CRVO with the same treatment. RESULTS--About 66% of the younger patients were men compared to only 46% in older patients. At least two cardiovascular risk factors were present in 8.5% of the younger and 54% of the older patients. 16 eyes showed the ischemic, 19 the nonischemic type of CRVO, a similar distribution as in older patients. The course of the disease was more favourable in younger patients, although ocular complications may occur in ischemic CRVO. Isovolemic hemodilution did not change the initial visual acuity of eyes with nonischemic CRVO, but led to an improvement in 56% of the eyes with ischemic CRVO. This means only a minor difference to the course of CRVO in hemodiluted older patients. CONCLUSION--In general, there is no principal difference between the CRVO in younger and older patients, but the course is more favourable in younger patients. On the basis of these findings we recommend isovolemic hemodilution in younger patients with ischemic CRVO.

Aim To conduct a systematic review in order to compare adverse effects (AE) and the reporting of harm in randomised controlled trials (RCTs) and non-RCTs evaluating intravitreal ranibizumab and bevacizumab in age-related macular degeneration. Methods Medline, Embase and the Cochrane Library were searched with no limitations of language and year of publication. Studies which compared bevacizumab or ranibizumab as monotherapy with any other control group were included. Case series were included if they met predefined quality standards. Results The 2 year results of phase III trials evaluating ranibizumab show that the rates of serious ocular AE were low (≤2.1%) but indicate major safety concerns (RR 3.13, 95% CI 1.10 to 8.92). A possible signal with regard to thromboembolic events (RR 1.35, 95% CI 0.66 to 2.77) and a significant increase in non-ocular haemorrhage (RR 1.62, 95% CI 1.03 to 2.55) were also noted. In contrast to ranibizumab trials, the RCTs evaluating bevacizumab are of limited value. The main shortcomings are small sample sizes and an apparent lack of rigorous monitoring for AE. A critical assessment of the large number of published case series evaluating bevacizumab also shows that no reliable conclusions on safety can be drawn using this study design. Therefore, any perception that intravitreal bevacizumab injections are not associated with major ocular or systemic AE are not supported by reliable data. Conclusion The bevacizumab studies show too many methodological limitations to rule out any major safety concerns. Higher evidence from ranibizumab trials suggests signals for an increased ocular and systemic vascular and haemorrhagic risk which warrants further investigation.

Purpose To determine the concentration of the pro-angiogenic vascular endothelial growth factor VEGF 165 (VEGF) and the anti-angiogenic VEGF 165b in vitreous samples of patients with branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) in comparison to patients without retinal occlusive disease. Design Experimental laboratory investigation. Methods Vitreous samples were collected from patients undergoing surgery for arteriovenous dissection after BRVO, radial optic neurotomy after CRVO in the occlusion group, or macular pucker or macular hole in the control group. Concentrations of VEGF and VEGF 165b were determined by ELISA and an ELISA-type antibody microarray. Results Average vitreal concentration of VEGF was 8.6 ng/mL in the CRVO group and 2.0 ng/mL in the BRVO group as compared to 0.26 ng/mL in the control group. Average vitreal concentration of VEGF 165b was 27 pg/mL in the CRVO group, 42 pg/mL in the BRVO group, and 49 pg/mL in the control group. In patients with CRVO and BRVO, the angiogenic balance was shifted towards angiogenic stimulation. Conclusion The severity of RVO from BRVO to CRVO correlates with an increase of VEGF and the decrease of VEGF 165b , indicating a pro-angiogenic shift. Altering the ratio of VEGF 165b /VEGF 165 might be a feasible approach for treating retinal occlusive diseases.

Purpose of review We conducted a systematic review to evaluate whether the existing evidence justifies the intravitreal use of bevacizumab in comparison to ranibizumab in age-related macular degeneration. Recent findings Compared with photodynamic therapy, bevacizumab shows a relative improvement in visual acuity that is of similar size as in the comparison of ranibizumab with photodynamic therapy (relative improvement from 30 to 35%). However, this finding is based on one randomized controlled trial including less than 50 patients treated with bevacizumab. Also, nothing is known about long-term (>12 months) improvements in visual acuity and optimal treatment intervals for bevacizumab.Regarding safety, the published literature indicates that ocular and systemic adverse effects are less frequent under bevacizumab than ranibizumab treatment. But the validity of this finding is strongly limited by inadequate reporting, an unsystematic evaluation of adverse effects and short follow-up times in studies evaluating bevacizumab. Summary Given the lack of controlled data, the widespread off-label use of bevacizumab is not justified in clinical practice. On the other hand, a major challenge in the management of patients who require repeated antivascular endothelial growth factor injections is the high cost of ranibizumab. This dilemma underlines the need for head-to-head studies comparing both vascular endothelial growth factor antibodies, or, at least, well conducted randomized controlled trials evaluating intravitreal bevacizumab.

Acta Ophthalmol. 2011: 89: 82–90 Abstract. Purpose: To investigate whether EphrinB2 (EfnB2) or EphB4 influence retinal angiogenesis under physiological or pathological conditions. Methods: Using the mouse model of oxygen-induced proliferative retinopathy (OIR), the expression of EfnB2, EphB4, vascular endothelial growth factor (VEGF), VEGFR1 and VEGFR2 was quantified by quantitative polymerase chain reaction (qPCR) and localized in EfnB2- and EphB4-lacZ mice. Angioproliferative retinopathy was manipulated by intravitreal injection of dimeric EfnB2 and monomeric or dimeric EphB4. Results: Dimeric EphB4 (EphB4-Fc) and EfnB2 (EfnB2-Fc) enhanced hypoxia-induced angioproliferative retinopathy but not physiological angiogenesis. Monomeric EphB4 (sEphB4) reduced angiogenesis. The messenger RNA (mRNA) level of EfnB2 increased significantly in the hyperoxic phase (P7–P12), while EphB4, VEGF, VEGFR1 and VEGFR2 showed a significant – up to fivefold – increased expression at P14, the start of morphologically visible vasoproliferation caused by relative hypoxia. Conclusion: The ephrin/Eph system is involved in angioproliferative retinopathy. Stimulation of EphB4 and EfnB2 signalling using EfnB2-Fc and EphB4-Fc, respectively, enhanced hypoxia-induced angiogenesis. In contrast, sEphB4 inhibited hypoxia-induced angiogenesis. Therefore, angiogenesis is enhanced by signalling through both EphB4 (forward) and EfnB2 (reverse). The distinction in the expression kinetics of EphB4 and EfnB2 indicates that they govern two different signalling pathways and are regulated in diverse ways. sEphB4 might be a useful drug for antiangiogenic therapy.

Posterior herpes disease is rare in immunocompetent patients, yet it occurs in up to 40% of individuals with late stages of human immune deficiency virus (HIV) infection with severe immune suppression, and is then almost exclusively caused by the cytomegalovirus (CMV). It then follows, that the posterior part of the eye is much more often infected by the β subgroup of herpes viruses (CMV) than by α-herpes viruses (HSV, VZV). CMV retinitis is currently one of the most frequent single causes of posterior infection, at least in regions with high incidence of HIV, and with no access to modern antiretroviral treatment.

We developed a program for testing the central 12 degrees of the visual field with a spatial resolution of 1.6 degrees that was easy to operate. The program was designed for the Octopus computer-perimeter and created by means of the SARGON-utility. Our way of examining differed slightly from the standard Octopus procedure. We tested 16 normal eyes and 13 eyes of patients with various diseases of the central retina. Our normal values of differential threshold sensitivities were about 1.8 dB below the normal values of the Octopus system. Sensitivity and specificity of the program were nearly identical irrespective of using our normal values or the Octopus normal values for the calculation of the above mentioned parameters. Sensitivity was 84.6%, specificity 87.5%. The ability of the program to correctly localize retinal defects was shown. The program was designed for follow-up of patients having undergone paramacular lasercoagulation.

Choroidal neovascularisation (CNV) as a feature of exudative age-related macular degeneration (AMD) is partially regulated by retinal pigment epithelium (RPE). In this study, the effect of combinatory anti-angiogenic treatment was evaluated using a novel in vitro assay of RPE-induced angiogenesis. RPE isolated from surgically excised CNV-membranes (CNV-RPE) was used to stimulate sprouting of endothelial cell (EC) spheroids in a 3D collagen matrix. The anti-angiogenic effect of solitary anti-VEGF antibodies (bevacizumab) was compared to a combinatory treatment with anti-VEGF and anti-FGF2 antibodies. Anti-VEGF treatment inactivated all RPE-derived VEGF but was unable to fully inhibit EC sprouting induced by CNV-RPE. Combined anti-VEGF/anti-FGF treatment inactivated both growth factors and reduced EC sprouting significantly. RPE from CNV patients expresses angiogenic growth factors that act in part independently of VEGF. Targeted combinatory therapy can be superior to solitary anti-VEGF therapy. One possible candidate for combinatory therapy is FGF2.

Introduction Retinal venous and arterial occlusions are common causes of visual loss. Depending on the location and extent, symptoms may vary from very discrete impairments to complete loss of sight.

A complicated well-regulated balance exists between the thrombosis and fibrinolysis systems. This chapter will cover the two main categories of retinal vascular occlusive disease (RVOD): central (CVO) or branch retinal vein occlusion (BVO) and central (CAO) or branch retinal artery occlusion (BAO). This chapter will not address the overall diagnostic evaluation of patients with retinal vascular disease. Patients with CAO/BAO should be evaluated by their medical doctor for common underlying causes such as ipsilateral carotid disease and heart disease. Patients with bilateral, simultaneous CVO/BVO of course should be evaluated for common causes of hypercoagulable states such as Waldenstrom’s or multiple myeloma. Basic evaluation should include a medical review of systems, testing for high blood pressure and diabetes for all patients, and sedimentation rate, carotid Doppler and cardiac sonogram should always be obtained for retinal arterial disease (RAO). After a basic evaluation, many patients with RAO or retinal venous disease (RVO) are said to have idiopathic conditions. In recent years, there have been a large number of papers citing possible associations of RAO and RVO with abnormalities of plasma proteins. Are these associations real? Which should be considered and looked for in which patients? It will be some years before we can offer clear guidance on this subject, and there is a strong need for large prospective studies with contemporaneous well-matched control groups. Until these studies are available, in this chapter we summarize the pertinent literature and offer some thoughts on whether and how patients with RAO and RVO who do not have obvious causes after a “basic” evaluation should be worked up.

The effect of the heparin analog 5-amino-2-naphthalenesulfonate (5-amino-2-NMS) on retinal neovascularization was investigated in the mouse model for oxygen-induced retinopathy (OIR). From postnatal day 7 (P7) until P12, mice were kept in a 75% oxygen environment. On P12, they received an intravitreal injection of 10mM 5-amino-2-NMS in one eye and PBS as control substance in the fellow eye. The animals were intracardially perfused with fluorescein-dextran solution on P17. Retinal whole mounts were prepared and ischemic retinopathy was evaluated in 30 animals using a standardized retinopathy score. A single intravitreal injection of 5-amino-2-NMS reduces significantly angioproliferative changes (blood vessel tufts, extra-retinal neovascularization, and blood vessel tortuosity) compared to the contralateral control eye (p=0.025). The median retinopathy score (maximal 13) for the 5-amino-2-NMS treated eyes was 6 versus 8 for the control eyes. 5-Amino-2-NMS binds to the heparin-binding site of FGF1 and FGF2 and thus may be a promising substance for the local treatment of retinal neovascularization.

Macular edema is the main reason for decreased visual acuity (VA) in early retinal vein occlusion (RVO). Bevacizumab (Avastin, Genentech) is an anti-VEGF substance to treat macular edema triggered by hypoxia-induced expression of vascular endothelial growth factor (VEGF). Initial reports showed a significant reduction of central retinal thickness and improved visual acuity (VA) after bevacizumab injection. To date, only retrospective studies and case reports have been published on bevacizumab treatment of RVO.In this prospective interventional case series, we evaluated the response to a single bevacizumab treatment in 21 RVO patients (14 CRVO, 7 BRVO). Study endpoints were visual acuity (VA) using ETDRS charts and central macular edema (CME) over 9 weeks.Mean VA from all 21 patients increased by more than 2 lines (2.4+/-0.4 lines; p0.01 compared to baseline). The improvement of VA after bevacizumab injection was concordant with a decrease in central retinal thickness. Peak VA was reached between 3 and 6 weeks after injection. Between week 6 and 9 a decrease in VA was observed. This VA decrease was precipitated by an increase in CME between week 3 and 6. In subgroup analyses, patients receiving bevacizumab injection within the first 3 months after RVO showed an average VA gain of 4 lines (range 2-7 lines) compared to an average gain of 1.8 (range 1-3) and 2.5 (range 1-7) in patients receiving bevacizumab between 4-6 months and after more than 6 months, respectively.Bevacizumab injection is able to improve CME and VA in RVO patients within the first 3 to 9 weeks. We did not observe any short-term adverse effects during our study. As the decrease in VA was anticipated by an increase in central retinal thickness, regular OCT examinations between week 3 and 6 may be helpful for judging the appropriate timing for re-injection in order to maintain patients within the initially reached range of VA until a new balance between inflow and outflow in the retinal circulation is reached.

PURPOSE: To evaluate the safety and efficacy of the COX-2 inhibitor valdecoxib in treating macular edema after cataract surgery. SETTING: University Eye Clinic, Freiburg, Germany and Reis Medical Institution, Liechtenstein. METHODS: The COX-2 inhibitor valdecoxib (Bextra) was administered systemically to patients with significant visual loss resulting from macular edema in a prospective clinical trial. RESULTS: Ten patients were enrolled. Valdecoxib was tolerated well and led to a significant visual improvement within 10 days of therapy in all patients. CONCLUSION: The fast and persistent control of macular edema with valdecoxib warrants further investigation.

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.Prospective interventional case series.Thirteen strictly defined patients with ischemic CRVO.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.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.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.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.

Purpose The visual acuity (VA) of patients with very low vision is classified using the semiquantitative scale "counting fingers" (CF), "hand motion" (HM), "light perception" (LP), and "no light perception." More quantitative measures would be desirable, especially for clinical studies. The results of clinical VA measurements, Early Treatment Diabetic Retinopathy Study (ETDRS) charts, and the Freiburg Visual Acuity Test (FrACT) were compared. The FrACT is a computerized visual acuity test that can present very large Landolt C optotypes when necessary. Methods Examined were 100 eyes of 100 patients with various eye diseases (e.g., diabetic retinopathy, ARMD), covering a range of VAs from LP to decimal 0.32. The FrACT optotypes were presented on a 17-inch LCD monitor with random orientation. After extensive training, two ETDRS and FrACT measurements were obtained. The testing distance was 50 or 100 cm. Results ETDRS and FrACT coincided closely for VA > or = 0.02 (n = 80). ETDRS measures were successfully obtainable down to CF (at 30 cm; test-retest averaged over all patients, coefficient of variation [CV](ETDRS) = 9% +/- 8%), and FrACT provided reproducible measurements down to HM (test-retest CV(FrACT) =12% +/- 11%). For CF (n = 6), both ETDRS and FrACT resulted in a mean VA of 0.014 +/- 0.003 (range, 0.01-0.02). The VA results of FrACT for HM (n = 12) were 0.005 +/- 0.002 (range, 0.003-0.009); the individual values were highly reproducible. No results were obtainable for LP (n = 2). Conclusions The three acuity procedures concur above a VA of 0.02. The results suggest that the category CF at 30 cm can be replaced by 0.014, using ETDRS or FrACT. Using FrACT, one can even reproducibly quantify VA in the HM-range, yielding a mean VA of 0.005.