Progressive Optic Neuropathy Research Articles

The pathophysiology and treatment of glaucoma: a review.

Glaucoma is a worldwide leading cause of irreversible vision loss. Because it may be asymptomatic until a relatively late stage, diagnosis is frequently delayed. A general understanding of the disease pathophysiology, diagnosis, and treatment may assist primary care physicians in referring high-risk patients for comprehensive ophthalmologic examination and in more actively participating in the care of patients affected by this condition. To describe current evidence regarding the pathophysiology and treatment of open-angle glaucoma and angle-closure glaucoma. A literature search was conducted using MEDLINE, the Cochrane Library, and manuscript references for studies published in English between January 2000 and September 2013 on the topics open-angle glaucoma and angle-closure glaucoma. From the 4334 abstracts screened, 210 articles were selected that contained information on pathophysiology and treatment with relevance to primary care physicians. The glaucomas are a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and resulting changes in the optic nerve head. Loss of ganglion cells is related to the level of intraocular pressure, but other factors may also play a role. Reduction of intraocular pressure is the only proven method to treat the disease. Although treatment is usually initiated with ocular hypotensive drops, laser trabeculoplasty and surgery may also be used to slow disease progression. Primary care physicians can play an important role in the diagnosis of glaucoma by referring patients with positive family history or with suspicious optic nerve head findings for complete ophthalmologic examination. They can improve treatment outcomes by reinforcing the importance of medication adherence and persistence and by recognizing adverse reactions from glaucoma medications and surgeries.

Neurotrophic factors for retinal ganglion cell neuropathy - with a special reference to diabetic neuropathy in the retina.

Diabetes mellitus is a disease with a devastating impact on population. Recent data revealed that early retinal neuropathy in patients with diabetic retinopathy involved a reduced expression of brain-derived neurotrophic factor. Retinal ganglion cells (RGC) neuropathy is a progressive optic nerve neuropathy with RGC death and axonal degeneration, and it leads to blindness in the elderly population worldwide. Thus, neuroprotective therapies that rescue damaged RGCs and inhibit the progression of RGC loss and axonal degeneration are needed. This review introduces potential neuroprotective therapies using different neurotrophic factors for damaged RGC in eyes with RGC neuropathy associated diseases.

Transcranial Orbital Decompression for Progressive Compressive Optic Neuropathy After 3-Wall Decompression in Severe Graves’ Orbitopathy

To determine surgical outcomes after transcranial decompression of the superior orbit in patients with progressive compressive optic neuropathy (CON) secondary to Graves' orbitopathy (GO) who had previously been treated with 3-wall decompression. Approval from the West Virginia University Institution Review Board was obtained. A retrospective review of 4 patients with GO who received bilateral transcranial decompression of the orbits for progressive compressive optic neuropathy after bilateral maximal extracranial 3-wall decompression was performed. The patients were treated by the Multidisciplinary Orbit and Skull Base Services at West Virginia University and the University of Michigan. Bilateral transcranial decompression of the orbit for GO was performed on 8 orbits in 4 patients. All 8 orbits had radiographic evidence of compression of the orbital apex, and all patients had been treated with steroids, orbital radiation, and bilateral 3-wall decompression. Preoperative vision ranged from 20/25 to 20/100, which improved to 20/25 or better in all eyes. The visual field mean deviation improved from a mean of -13.05 to -1.67 dB. Hertel measurements improved from a mean of 19.25 to 15.25 mm. Extraocular motility was essentially unchanged. Two patients were noted to have asymptomatic ocular pulsations. There were no other complications, and all patients remained stable during a follow-up period of 5 years (range 2-8 years). Transcranial decompression is an effective and safe method of salvaging vision when standard treatments fail. This is only the second report of transcranial decompression for refractory compressive optic neuropathy after decompression from a standard approach.

Nanomedicine for glaucoma: sustained release latanoprost offers a new therapeutic option with substantial benefits over eyedrops.

Glaucoma is a chronic progressive optic neuropathy that is characterized by optic nerve changes and visual field loss. Elevated intraocular pressure (IOP) is the main modifiable risk factor. Chronic instillation of daily eyedrops to lower IOP is the primary treatment of choice, although it requires patient adherence and correct performance. We have developed a nanoliposome drug delivery system for the longer term delivery of latanoprost. In the present open-label, pilot study, the safety and efficacy of a single subconjunctival injection of liposomal latanoprost was evaluated in six subjects with a diagnosis of either ocular hypertension (OHT) or primary open-angle glaucoma (POAG). Subconjunctival injection of liposomal latanoprost was well tolerated by all six subjects. From a baseline IOP of 27.55 ± 3.25mmHg, the mean IOP decreased within 1h to 14.52 ± 3.31mmHg (range 10-18mmHg). This represented a mean decrease of 13.03 ± 2.88mmHg (range 9-17mmHg), or 47.43 ± 10.05% (range 37-63%). A clinically and statistically significant IOP reduction (≥20% IOP reduction, P = 0.001 to 0.049) was observed through 3months after injection. The nanomedicine reported here is the first nanocarrier formulation that has an extended duration of action in humans, beyond a couple of weeks. The findings in this study open up a new treatment modality, which will greatly enhance patient compliance and improve treatment outcomes. The current study provides the evidence and support for further clinical studies of liposomal latanoprost in the treatment of glaucoma.

Trabeculectomía, una terapia vigente: estudio observacional descriptivo en el Hospital Universitario San Ignacio en Bogotá

Introducción: el glaucoma es una enfermedad del nervio óptico de carácter crónico y progresivo que constituye un problema epidemiológico serio, ya que es responsable de la segunda causa de ceguera irreversible en el mundo. Existen diferentes modalidades de tratamiento, entre ellos medicamentos, láseres y cirugías. La trabeculectomía es el procedimiento quirúrgico de elección en el paciente adulto cuando la terapia médica y los procedimientos con láser fracasan en detener esta neuropatía óptica.Objetivo: analizar una serie de pacientes sometidos a trabeculectomía en el Hospital San Ignacio entre el 2005 y el 2011.Conclusión: los resultados, a pesar de ser una serie pequeña de pacientes, nos permiten afirmar que dicha cirugía continúa siendo una buena alternativa en el control de la presión intraocular y, por consiguiente, en la progresión del daño glaucomatoso sobre el nervio óptico.

Optic Nerve Sheath Decompression

The purpose of this study was to determine the safety and efficacy of optic nerve sheath decompression (ONSD) with a medial transconjunctival approach for a variety of indications in a larger population of patients than has previously been reported. A retrospective chart review was performed on consecutive patients who underwent ONSD between January 1992 and December 2010. Before ONSD, all patients had documented evidence of progressive loss of visual acuity or visual field, or both. Postoperative follow-up visits were scheduled at 1 week, 1 month, and then every 3-6 months. Main outcome measures were visual acuity, visual fields, and surgical complications. Five hundred seventy-eight eyes of 331 patients underwent ONSD for progressive vision loss due to various indications, which included but were not limited to idiopathic intracranial hypertension (IIH), progressive nonarteritic ischemic optic neuropathy, and optic nerve drusen (OND). During a mean follow-up of 18.7 months (range, 1 week to 10 years), postoperative visual acuity remained stable or improved in 536 of 568 eyes (94.4%) and progressively worsened in 32 of 568 eyes (5.6%). Visual fields remained stable or improved in 257 of 268 eyes (95.9%) and progressive visual field loss occurred in 11 of 268 eyes (4.1%). There were no reported intraoperative complications. The most common postoperative complication was diplopia (6.0%). To our knowledge, this review represents the largest series of patients who have undergone ONSD for any indication. Our data are consistent with current literature supporting ONSD as a safe and effective procedure for IIH. Other indications for ONSD, such as progressive visual field loss associated with OND, warrant further study. Regardless of the indication, complications following ONSD with the technique described in this report are infrequent.

New directions in the treatment of normal tension glaucoma.

Glaucoma is a progressive optic neuropathy that causes characteristic changes of the optic nerve and visual field in relation to intraocular pressure (IOP). It is now known that glaucoma can occur at statistically normal IOPs and prevalence studies have shown that normal tension glaucoma (NTG) is more common than previously thought. While IOP is believed to be the predominant risk factor in primary open angle glaucoma (POAG), IOP-independent risk factors, such as vascular dysregulation, are believed to play an important part in the pathogenesis of NTG. Though certain distinguishing phenotypic features of NTG have been reported, such as an increased frequency of disc hemorrhages, acquired pits of the optic nerve and characteristic patterns of disc cupping and visual field loss, there is much overlap of the clinical findings in NTG with POAG, suggesting that NTG is likely part of a continuum of open angle glaucomas. However, IOP modification is still the mainstay of treatment in NTG. As in traditional POAG, reduction of IOP can be achieved with the use of medications, laser trabeculoplasty or surgery. Studies now show that the choice of medication may also be important in determining the outcomes of these patients. Though it is likely that future treatment of NTG will involve modification of both IOP and IOP-independent risk factors, current efforts to develop IOP-independent neuroprotective treatments have not yet proven to be effective in humans.

Cellular stress response, redox status, and vitagenes in glaucoma: a systemic oxidant disorder linked to Alzheimer's disease.

Amyloid deposits, constituted of amyloid beta (Aβ) aggregates, are a characteristic feature of several neurodegenerative diseases, such as Alzheimer’s, mild cognitive impairment and Parkinson’s disease. They also have been recently implicated in the pathogenesis of retinal damage, as well as age-related macular degeneration and glaucoma. Glaucoma is a progressive optic neuropathy characterized by gradual degeneration of neuronal tissue due to retinal ganglion cell loss, associated to visual field loss over time resulting in irreversible blindness. Accumulation of Aβ characterizes glaucoma as a protein misfolding disease, suggesting a pathogenic role for oxidative stress in the pathogenesis of retinal degenerative damage associated to glaucoma. There is a growing body of evidence demonstrating a link between Alzheimer’s disease and glaucoma. Further, several heat shock proteins (HSPs) members have been implicated both in neurodegenerative diseases and glaucomatous apoptosis. To maintain redox homeostasis vitagenes, as integrated mechanisms, operate actively to preserve cell survival under condition of stress. Vitagenes encode for sirtuin, thioredoxin and HSPs. The present study was designed to investigate cellular stress response mechanisms in the blood of patients with glaucoma, compared to control subjects. Levels of vitagenes HSP-72, heme oxygenase-1, as well as F2-isoprostanes were significantly higher in the blood of patients with glaucoma than in controls. Furthermore, in the same experimental group increased expression of Trx and sirtuin 1 were measured. Our results sustain the importance of redox homeostasis disruption in the pathogenesis of glaucoma and highlights the opportunity that new therapies that prevents neurodegeneration through non-immunomodulatory mechanisms might be synergistically associated with current glaucoma therapies, thus unraveling important targets for novel cytoprotective strategies.

Scanning laser polarimetry in glaucoma.

Glaucoma is an acquired progressive optic neuropathy which is characterized by changes in the optic nerve head and retinal nerve fiber layer (RNFL). White-on-white perimetry is the gold standard for the diagnosis of glaucoma. However, it can detect defects in the visual field only after the loss of as many as 40% of the ganglion cells. Hence, the measurement of RNFL thickness has come up. Optical coherence tomography and scanning laser polarimetry (SLP) are the techniques that utilize the evaluation of RNFL for the evaluation of glaucoma. SLP provides RNFL thickness measurements based upon the birefringence of the retinal ganglion cell axons. We have reviewed the published literature on the use of SLP in glaucoma. This review elucidates the technological principles, recent developments and the role of SLP in the diagnosis and monitoring of glaucomatous optic neuropathy, in the light of scientific evidence so far.

Controllable Urokinase Gene Expression in Trabecular Meshwork Cells

Purpose: Glaucoma is a type of progressive optic neuropathy that finally leads to blindness related to elevated intraocular pressure (IOP). Accumulation of extracellular matrix in trabecular meshwork (TM) and juxta-canalicular connective tissues, which form an aqueous outflow pathway, may be a major cause of increased IOP, thus the fibrinolytic system may be associated with regulation of IOP. We examined the possibility of controllable urokinase plasminogen activator (uPA) gene transfer into TM cells.Methods: TM cells were freshly isolated from porcine eyes and human TM cells obtained during trabeculectomy procedures and cultured. Total RNA was extracted from human TM cells and reverse transcribed into cDNA. A reverse-transcribed polymerase chain reaction (RT-PCR) method was then performed to detect the gene expression of uPA. The cDNA of human uPA was sub-cloned into an expression vector (pEYFP-N1 vector) and controllable expression vector (TRE-Tight vector), then each vector was independently transfected into cultured porcine TM cells. Doxycycline was added to the culture medium to activate the pTet-ON and TRE-Tight vectors. Finally, the expression of uPA was examined using an enzyme linked immunosorbent assay (ELISA).Results: ELISA findings revealed the expression of uPA (3.5 ng/ml) in medium from cultured porcine TM cells that had been transfected with the human uPA gene using the pEYFP-N1 vector. Doxycycline induced human uPA in the pTet-On and TRE-Tight vectors with human uPA gene co-transfected TM cells in a dose-dependent manner.Conclusions: Controllable gene transfer of uPA, which may degrade the extracellular matrix in juxta-canalicular connective tissue, into TM cells was achieved using a Tet-On system. The present method may be useful as a novel therapy for glaucoma.

Emerging Trabecular Outflow Drugs

Emerging Trabecular Outflow Drugs

Optic neuropathy in Behçet’s syndrome

This paper presents the clinical features, investigation results and response to treatment of four cases of primary optic neuropathy in Behçet's syndrome, with a comprehensive literature search for all other published cases. A total of 20 cases has been identified; the clinical syndrome is a unilateral or bilateral optic neuropathy of inflammatory type in which pain arises in 20 % and optic disc swelling seen in 45 % of cases. The condition was relapsing in four cases, and a progressive optic neuropathy was seen in one case. All but the progressive case responded to steroids with or without additional immunosuppression. The nadir visual acuity was the only determinant of visual outcome. 67 % of cases reported a return to normal acuity following treatment.

The vast complexity of primary open angle glaucoma: Disease genes, risks, molecular mechanisms and pathobiology

Primary open angle glaucoma (POAG) is a complex progressive optic nerve neuropathy triggered by both environmental and genetic risk factors. Several ocular tissues, including the ciliary body, trabecular meshwork and optic nerve head, and perhaps even brain tissues, are involved in a chain of pathological events leading to POAG. Genetic risk evidence for POAG came from family linkage-studies implicating a small number of disease genes (MYOC, OPTN, WDR36). Recent Genome Wide Association Studies (GWAS) identified a large number of new POAG loci and disease genes, such as CAV1, CDKN2B and GAS7. In the current study, we reviewed over 120 family and GWA studies. We selected in total 65 (candidate) POAG disease genes and proceeded to assess their function, mRNA expression in POAG relevant eye tissues and possible changes in disease state. We found that the proteins corresponding to these 65 (candidate) POAG disease genes take part in as few as four common functional molecular networks. Functions attributed to these 4 networks were developmental (dys)function, lipid metabolism, and inflammatory processes. For the 65 POAG disease genes, we reviewed the available (transgenic) mouse models of POAG, which may be useful for future functional studies. Finally, we showed that the 65 (candidate) POAG genes substantially increased the specificity and sensitivity of a discriminative POAG risk test. This suggests that personal risk assessment and personalized medicine for POAG are on the horizon. Taken together, the data presented are essential to comprehend the role of genetic variation in POAG, and may provide leads to understand the pathophysiology of POAG as well as other neurodegenerative disorders, such as Alzheimer's disease.

A comparative study of Xalatan and Xalacom (Pfizer, USA) efficacy in the treatment of pseudoexfoliative glaucoma

The purpose of this study was to compare the efficacy of Xalatan (Pfizer, USA) and Xalacom (Pfizer, USA) in pseudoexfoliative glaucoma therapy. We observed 41 patients (53 eyes) with PEG, 16 of them were men and 25 women. Treatment period was 24 months. The main group (20 patients, 28 eyes) instilled Xalatan, the comparison group (21 patients, 25 eyes) instillated Xalacom once before bedtime (8 p. m.). In the Xalatan group, IOP decreased from 23.75 ± 0.576 mm Hg at baseline to 18.93 ± 0.337 mm Hg at 6 Month visit, and increased again up to 22.00 ± 0,542 mm Hg by the end of 24 months period. In the Xalacom group, IOP decreased from 22.00 ± 0.552 at baseline to 19.67 ± 0.47 at 6 Months visit and did not increase significantly to the 24 Month visit. Glaucoma stabilization was registered in both groups. MD index improved at 12 Months visit from –5.16 ± 0.61 to –4.21 ± 0.66, without significant changes till Visit 24 Month in the Xalatan group. MD index improved for the entire period of observation from –5.57 ± 0.64 to 4.82 ± 0.69 in the Xalatan group. These results allow us to recommend Xalatan and Xalacom as medications of choice for PEG treatment, especially taking into consideration possible risk of glaucomatous optic neuropathy progression.

Idiopathic Sclerosing Orbital Inflammation

We read with great interest the report by Levin et al (1) regarding the role of the optic nerve biopsy in the management of progressive optic neuropathy. We had the opportunity to evaluate a 50-year-old man with progressive deterioration of vision in his left eye for 2 months with minimal periocular pain. Visual acuity was 20/20, right eye, and no light perception, left eye. The right fundus was normal but there was marked optic disc edema in the left eye (Fig. 1). Magnetic resonance imaging (MRI) of the brain and orbits demonstrated enhancement and thickening of the left optic nerve (Fig. 2). An extensive work-up including hematologic tests, lumbar puncture, and computed tomography of chest, abdomen, and pelvis was unremarkable. The patient was given 1 g of methylprednisolone intravenously for 3 days followed by a tapering dose of oral steroids over several months. Although there was improvement in the left optic disc edema, vision remained unchanged.FIG. 1: Left fundus shows marked optic disc edema with peripapillary hemorrhages.FIG. 2: Postcontrast axial (A) and coronal (B) T1 magnetic resonance imaging with fat suppression shows thickening and enhancement of the left optic nerve.Four months after onset of symptoms, the patient reported vision loss in the right eye. Acuity was 20/40, right eye, and no light perception, left eye. Funduscopy revealed right optic disc edema and left optic atrophy. MRI demonstrated thickening of the right optic with marked enhancement following intravenous contrast. Prednisone was restarted at a dose of 1 mg/kg/d, and there was rapid improvement in the vision in the right eye with resolution of right optic disc edema. Given involvement of the previously unaffected right eye, a biopsy of the left optic nerve was performed. Histopathology showed primarily fibrosis and an inflammatory infiltrate consisting of lymphocytes, histiocytes, and plasma cells (Fig. 3). No granulomas were identified. Stains for infectious, immune, and neoplastic disorders were nondiagnostic. Based on these results, a diagnosis of idiopathic sclerosing orbital inflammation (ISOI) was made.FIG. 3: Biopsy demonstrates optic nerve and sheath fragments with marked fibrosis accompanied by an inflammatory infiltrate of lymphocytes, histiocytes, and plasma cells (periodic acid–Schiff, ×400).ISOI is a rare condition characterized by marked fibrosis and some inflammatory infiltrate (2–4). However, unlike idiopathic orbital inflammation, which has an acute clinical onset, the progression of ISOI generally has a chronic and indolent course (5). In our patient, there was consecutive involvement of both optic nerves. There are reports of ISOI associated with systemic idiopathic fibrosis and increased serum levels of IgG4 (6,7). Our patient did not show increased serum levels of IgG4, and the biopsy specimen was negative for the presence of IgG4.

Critical Assessment of Implantable Drug Delivery Devices in Glaucoma Management

Glaucoma is a group of heterogeneous disorders involving progressive optic neuropathy that can culminate into visual impairment and irreversible blindness. Effective therapeutic interventions must address underlying vulnerability of retinal ganglion cells (RGCs) to degeneration in conjunction with correcting other associated risk factors (such as elevated intraocular pressure). However, realization of therapeutic outcomes is heavily dependent on suitable delivery system that can overcome myriads of anatomical and physiological barriers to intraocular drug delivery. Development of clinically viable sustained release systems in glaucoma is a widely recognized unmet need. In this regard, implantable delivery systems may relieve the burden of chronic drug administration while potentially ensuring high intraocular drug bioavailability. Presently there are no FDA-approved implantable drug delivery devices for glaucoma even though there are several ongoing clinical studies. The paper critically assessed the prospects of polymeric implantable delivery systems in glaucoma while identifying factors that can dictate (a) patient tolerability and acceptance, (b) drug stability and drug release profiles, (c) therapeutic efficacy, and (d) toxicity and biocompatibility. The information gathered could be useful in future research and development efforts on implantable delivery systems in glaucoma.

OPA1 in mitochondrial quality control and its implications for RGC degeneration

AbstractMitochondria are vulnerable to damages of their proteins, lipids, and mtDNA by various stress factors and mitochondria either recycle dysfunctional mitochondria via the mitochondrial autophagy pathway, arrange for the recycling of the complete host cell by apoptosis, or continue to function normally and supply the host with energy and metabolites. This is called mitochondrial quality control and it is crucial for all neurodegenerative diseases, including the most prominent ones, Alzheimer’s disease and Parkinson’s disease. Mitochondrial quality control is facilitated by mitochondrial network dynamics – continuous fission and fusion of mitochondria. Mitochondrial fission is accomplished by DRP1. MFN1 and MFN2 on the mitochondrial outer membrane, and OPA1 on the mitochondrial inner membrane are necessary for mitochondrial fusion. Mitochondrial network dynamics are regulated in highly sophisticated ways by post‐translational modifications and protein processing. I would like to present selected aspects of mitochondrial quality control using OPA1 as an example and discuss their implication on Dominant Optic Atrophy, a slowly progressive optic neuropathy with juvenile onset caused by mutations in the OPA1 gene.

Fibrotic alterations in glaucoma

AbstractGlaucoma is the second leading cause of irreversible blindness worldwide, thought to affect 60 million people. It is a chronic progressive optic neuropathy with characteristic changes in the optic nerve head and subsequent visual field defects. In glaucoma, the lamina cribrosa (LC) region undergoes thickening and posterior migration in the early stages of the disease process, and later undergoes shearing and collapse of the LC plates leading finally to a thin fibrotic connective tissue structure/scar. This is characterised by the build‐up of extracellular matrix material and it is thought that this accumulation eventually results in elevated intraocular pressure and subsequent nerve damage. Here, we directly address the ongoing fibrotic pathology by use of alpha‐smooth actin expressing (myofibroblast‐like) human primary LC cells, including mechanisms of fibrosis and potential anti‐fibrotic therapies. Additionally we discuss the potential role of the Retinal Pigment Epithelial cell as a mediator of glaucomatous optic disc cupping / fibrosis through epithelial to mesenchymal transition.

Neuroprotection in glaucoma

Glaucoma is a frequent eye disease in the elderly and the second leading cause of irreversible blindness both in developed and developing countries (Resnikoff et al. 2004). Presently, about 50 million people are blind from glaucoma worldwide, a number that has not significantly changed over the last decade (Resnikoff et al. 2004; Thylefors et al. 1995). Without a doubt, glaucoma remains an unsolved problem of high significance in ophthalmology. Glaucoma is characterized by a chronic, progressive optic neuropathy that occurs in parallel to the formation of a typical excavation of the optic nerve head. The primary damage is restricted to retinal ganglion cells and the location of initial damage appears to be at the optic disc where their axons exit the eye. For a long time, intraocular pressure (IOP) had been suspected to cause or to contribute to axonal damage in glaucoma and since Adolph Weber introduced pilocarpine as an IOP-lowering therapy in 1876 (Weber 1876), medical therapy of glaucoma has been aimed at reducing IOP. This concept was challenged more recently, because of the observation that a significant percentage (up to 30–50 %) of patients suffering from glaucomatous neurodegeneration (Shiose et al. 1991; Anderson 2003) have IOPs in the statistically normal range of 10–21 mmHg (mean±2SD: 15.5±5.5 mmHg). Evidence for a causative or contributing role of IOP has finally been obtained through a number of randomized prospective multi-center studies that clearly identified IOP as the major risk factor for the pathogenesis of glaucoma (Collaborative Normal-Tension Glaucoma Study Group 1998a, b; Gordon et al. 2002; Kass et al. 2002; Leske et al. 2003; The AGIS Investigators 2000). Apparently, therapy that reduces IOP in patients with glaucoma is neuroprotective in the sense that it delays the structural and functional damage of retinal ganglion cell perikarya and their axons. Still, compliance to medical therapy is often unsatisfactory as daily eye-drop application is required (Reardon et al. 2011; Sleath et al. 2011). Although most patients are first treated with medical therapy, IOP-lowering operations come into play when medical therapy is no longer efficient, or when the patient is incompliant or does not tolerate topical eye drops. Presently, a large array of surgeries is available, all of which try to provide IOP reduction more than medical therapy can achieve with minimal surgical side effects. The advantage of the most effective surgical procedures is that very low IOPs (approx. 10–12 mmHg) can be achieved. In this respect, glaucoma surgery is the strongest neuroprotective measure on the basis of IOP lowering. However, surgery in glaucoma may not be successful, because of surgical complications and inappropriate wound healing. Moreover, there are only a limited number of randomized clinical trials assessing the success of surgical procedures in glaucoma (Coleman 2012). Considering the current limits of glaucoma therapy, there is need for the development of novel and alternative treatment strategies that save retinal neurons from glaucomatous injury or have the potential to repair neurons that have already been damaged. This Special Issue is aimed at providing a synopsis of therapeutically strategies with the potential to act neuroprotectively in glaucoma and independently from the reduction of IOP. Another purpose of the Special Issue is to review the obstacles that make the translation of experimental neuroprotective therapies into clinical practice E. R. Tamm (*) Institute of Human Anatomy and Embryology, University of Regensburg, Universitatstr. 31, 93053 Regensburg, Germany e-mail: Ernst.Tamm@vkl.uni-regensburg.de

Exceptions that Prove the Rules in Neuro-Ophthalmology

Exceptions that Prove the Rules in Neuro-Ophthalmology