Cochrane Systematic Review: Randomised Clinical Trials on Treatment for Normal Tension Glaucoma

Research project P 14266 Interventions for Normal Tension Glaucoma Hans-Georg EICHLER 08.05.2000 The aim of the study is to state evidence for pharmacological and/or surgical treatment of normal tension glaucoma because the treatment of this disease seems to be guided by individual preferences, habits and opinions but there are no well- established guidelines based on evidence. With this systematic review we intend to provide an unbiased, up to date summary of what we know and do not know about the different forms of medical treatment for normal tension glaucoma. Questions: Is pharmacological and/or surgical treatment able to reduce the progression of visual field loss and preserve visual acuity in patients with normal tension glaucoma? Does it lower the intraocular pressure, increase the retinal, choroidal or optic disc blood flow, or even improve visual field? We considered the assessment of visual field and visual acuity loss to be "hard" outcome measures whereas the intraocular pressure, increase of retinal, choroidal or optic disc blood flow were considered to be "soft" outcome measures. Background: Open angle glaucoma is a neuropathy of the optic nerve head which is characterized by specific alterations of the optic nerve morphology, irreversible visual field loss and in many cases an increased intraocular pressure (IOP). In contrast, normal tension glaucoma (NTG) is a clinical condition in which the optic nerve is pathologically excavated and the visual field is characteristically disturbed, although the intraocular pressure (IOP) is in the normal range. Today the following diagnostic criteria are widely used: A mean IOP off treatment 21 mm Hg or median IOP 20 mm Hg on diurnal testing, with no single measurement greater than 24 mm Hg; Open drainage angles on gonioscopy; Typical optic disc damage with glaucomatous cupping and loss of neuroretinal rim; Absence of any secondary cause for glaucomatous optic neuropathy; Visual field defect compatible with glaucomatous cupping. The natural course of the normal tension glaucoma is progressive visual loss. In a recent study 35% of randomized untreated eyes in a five years follow-up showed deepening of an existing scotoma, expansion of an existing scotoma, a new or expanded threat to fixation or a fresh scotoma in a previously normal part of visual field, in a way that they reached the endpoints defined by the authors and were treated according to the individual clinican`s decision (Collaborative Normal Tension Glaucoma Study Group 1998).The rate of visual field loss may vary from no dedectable change in retinal sensitivity over a period of 10 years or more, to upwards of 5 dB loss at individual retinal points a year (Kamal 1998). Since the first description of NTG (Graefe von 1857) it has been a diagnostic and therapeutic dilemma to physicians. There is a large spectrum of therapeutic interventions used for treatment of NTG which can be divided on the one hand into pharmacological or surgical, and on the other hand into IOP lowering or retinal, choroidal or optic nerve head blood flow increasing therapies. For all types of intervention there is a long list of either pharmacological agents or surgical techniques partly combined with the latter. The use of these therapeutic interventions seems to be guided by individual preferences, habits and opinions but there are no well-established guidelines based on evidence. As the effect of medical treatment on the progression of visual field loss of NTG patients is suggested to be small the most powerful form of evidence is needed to control for bias and random effects in order to be able to show clear benefit. Methods: Methods for identification of studies, study selection and data extraction and analysis will follow the guidelines for creating systematic reviews established by the Cochrane Collaboration. Briefly, trials will be identified from Medline, Embase, Biosis previews, the Cochrane controlled trial register, Cochrane Eyes and Vision Group register, Science Citation Index, searching of reference lists, contact with experts, investigators and pharmaceutical companies for unpublished studies. All randomised controlled trials where pharmacological and/or surgical interventions have been used to decrease the progression of visual field loss or to preserve visual acuity ( or to improve visual field (short term or long term), to lower IOP or to increase retinal, choroidal, or optic disk blood flow) in patients with the diagnosis NTG will be used. Studies will be selected independently by at least two reviewers. Two reviewers will independently extract data using a standardised form developed by the Cochrane Eyes and Vision Group. Discrepancies will be resolved by discussion and/or additional referees. Where appropriate, odds ratios will be summarised, after testing for heterogeneity between studies. Sensitivity analyses will be undertaken to determine the impact of study quality on effect size.

Normal tension glaucoma (NTG) is a clinical condition in which the optic nerve is pathologically excavated and the visual field is characteristically disturbed, although the intraocular pressure (IOP) is within the normal range. It is widely accepted that this optic nerve neuropathy results in progressive visual loss in most cases. There is some evidence that intraocular pressure plays a role in the progression of visual field defects in normal tension glaucoma patients. However, mechanisms of damage independent of intraocular pressure, such as vasospasm, reduced ocular blood flow, systemic hypotension and abnormal blood rheology may play a role as well. There are no well- established guidelines based on evidence for the treatment of normal tension glaucoma. This review aimed to assess the effects of different forms of medical and surgical treatment for normal tension glaucoma. This review included randomised controlled trials comparing different forms of medical or surgical therapy to placebo, no treatment, or other treatment. Interventions included the administration of medical or surgical therapy in any form and dosage with the intention to treat or to lower the rate of progression of symptoms in participants with normal tension glaucoma. A total of 13 randomised controlled trials were located that addressed interventions for NTG. Of these 5 trials were excluded. Analysis of these articles revealed that there is currently no evidence that medical or surgical treatment of normal tension glaucoma reduces the progression of the disease.