Neuroprotection for treatment of glaucoma in adults

Abstract

Background Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells and ultimately visual field loss. It is a leading cause of blindness worldwide. Open angle glaucoma (OAG), the commonest form of glaucoma, is a chronic condition that may or may not present with increased intraocular pressure (IOP). Neuroprotection for glaucoma refers to any intervention intended to prevent optic nerve damage or cell death. The treatment can target extracellular factors such as reducing IOP, or cellular factors derived from the optic nerve itself such as blocking intracellular death signals. Objectives The objective of this review was to systematically examine the evidence regarding the effectiveness of neuroprotective agents, either topical or oral, for slowing the progression of OAG in adults. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library, Issue 4, 2009), MEDLINE (January 1960 to January 2010), EMBASE (January 1980 to January 2010), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2010) and ClinicalTrials.gov (http://clinicaltrials.gov). (5 January 2010). There were no language or date restrictions in the search for trials. The electronic databases were last searched on 5 January 2010. Selection criteria This review was limited to randomized controlled trials (RCTs) in which topical or oral treatments were used to prevent retinal ganglion cell death. Our population of interest was adults with OAG. As the primary outcome for this review was the proportion of participants who developed any progression of visual field loss at five years post intervention, only trials with at least five years of follow-up were included. Data collection and analysis Two review authors independently reviewed titles and abstracts from the literature searches. Full text copies of relevant or potentially relevant studies were obtained and re-evaluated for inclusion. There were no trials identified for this review, thus we performed no data extraction or meta-analysis. Two studies comparing memantine to placebo are currently awaiting classification until additional study details are provided. Reasons for excluding studies from the review were documented. Main results In accordance with the selection criteria for inclusion, we identified no studies relevant for this review. The results of short-term trials and other studies are discussed in this review. Authors' conclusions Although neuroprotective agents are intended to act as pharmacological antagonists to prevent cell death, the evidence that they are effective in preventing retinal ganglion cell death, and thus preserving vision in patients with OAG, has not been demonstrated. Long-term RCTs are needed to determine whether or not neuroprotective agents may be beneficial for individuals with OAG.

Pharmacotherapy of Glaucoma

“…Although some smaller-scale studies have indicated that this may translate into visual field preservation, there is currently no sufficient evidence for a clinically meaningful neuroprotective effect, a conclusion that has recently also been drawn by a Cochrane Review on this subject. 95 Neuroprotection studies are difficult to perform for many reasons mentioned later in this review. One additional concern when comparing IOP-lowering drugs with regard to their visual field preserving effect arrives from IOP measurement itself, because lowering IOP at a certain time point does not necessarily result in a comparable 24 h IOP profile.…”

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

“…This Low-pressure Glaucoma Treatment Study (LoGTS) demonstrated a lower rate of progression of visual field loss in subjects treated with brimonidine compared to timolol, a beta-adrenergic antagonist which is not neuroprotective, but which lowered intraocular pressure in this study to a similar extent as brimonidine. This small study was critiqued for differential dropout, changes in the statistical analysis, and other issues (Cordeiro and Levin 2011;Sena and Lindsley 2013).…”

The Role of Serum Ceruloplasmin and Oxidative Stress Markers in Primary Open Angle Glaucoma

“…It is a progressive disease affecting people above 40 years, optic nerve changes are the main features, intraocular pressure (IOP) is the famous measurable risk factor for POAG, but some cases with the reduction of their IOP either by medical or surgical treatment does not stop the progression of the disease. So, other factors as lack of neurological protection for ganglion cells in the retina and cell apoptosis mechanisms may also play roles in progression of glaucoma [1] [2] [3]. Another factor may be incriminated in the process of POAG such as oxidative stress, other inflammatory factors and characteristic pattern of cell death by apoptosis [4].…”