- •PROGRESS IN BRAIN RESEARCH
- •List of Contributors
- •Preface
- •Epidemiology of primary glaucoma: prevalence, incidence, and blinding effects
- •Introduction
- •Prevalence of glaucoma
- •PAC suspect
- •PACG
- •Incidence of glaucoma
- •Blinding effects of glaucoma
- •Abbreviations
- •Acknowledgment
- •References
- •Predictive models to estimate the risk of glaucoma development and progression
- •Risk assessment in ocular hypertension and glaucoma
- •Risk factors for glaucoma development
- •Intraocular pressure
- •Corneal thickness
- •Cup/disc ratio and pattern standard deviation
- •The need for predictive models
- •Predictive models for glaucoma development
- •Predictive models for glaucoma progression
- •Limitations of predictive models
- •References
- •Intraocular pressure and central corneal thickness
- •Main text
- •References
- •Angle-closure: risk factors, diagnosis and treatment
- •Introduction
- •Mechanism
- •Other causes of angle closure
- •Risk factors
- •Age and gender
- •Ethnicity
- •Ocular biometry
- •Genetics
- •Diagnosis
- •Acute primary angle closure
- •Angle assessment in angle closure
- •Gonioscopy technique
- •Ultrasound biomicroscopy (UBM)
- •Scanning peripheral anterior chamber depth analyzer (SPAC)
- •Management
- •Acute primary angle closure
- •Medical therapy
- •Argon laser peripheral iridoplasty (ALPI)
- •Laser peripheral iridotomy (PI)
- •Lens extraction
- •Monitoring for subsequent IOP rise in eyes with APAC
- •Fellow eye of APAC
- •Chronic primary angle-closure glaucoma (CACG)
- •Laser peripheral iridotomy
- •Laser iridoplasty
- •Medical therapy
- •Trabeculectomy
- •Lens extraction
- •Combined lens extraction and trabeculectomy surgery
- •Goniosynechialysis
- •Summary
- •List of abbreviations
- •References
- •Early diagnosis in glaucoma
- •Introduction
- •History and examination
- •Quantitative tests and the diagnostic process
- •Pretest probability
- •Test validity
- •Diagnostic test performance
- •Posttest probability
- •Combing test results
- •Selective tests of visual function
- •Early glaucoma diagnosis from quantitative test results
- •Progression to make a diagnosis
- •Conclusions
- •Abbreviations
- •References
- •Monitoring glaucoma progression
- •Introduction
- •Monitoring structural damage progression
- •Monitoring functional damage progression
- •Abbreviations
- •References
- •Standard automated perimetry and algorithms for monitoring glaucoma progression
- •Standard automated perimetry
- •Global indices
- •HFA: MD, SF, PSD, CPSD
- •Octopus indices: MD, SF, CLV
- •OCTOPUS seven-in-one report (Fig. 2)
- •SAP VF assessment: full-threshold strategy
- •SAP VF defects assessment: OHTS criteria
- •SAP VF defects assessment: AGIS criteria
- •SAP VF defects assessment: CIGTS
- •Fastpac
- •Swedish interactive threshold algorithm
- •SAP VF assessment: the glaucoma staging system
- •SAP: interocular asymmetries in OHTS
- •SAP, VF progression
- •SAP: the relationship to other functional and structural diagnostic tests in glaucoma
- •SAP, FDP-Matrix
- •SAP, SWAP, HPRP, FDT
- •SAP: the relationship between function and structure
- •SAP, confocal scanning laser ophthalmoscopy, SLP-VCC
- •SAP, optical coherence tomography
- •SAP and functional magnetic resonance imaging
- •References
- •Introduction
- •Retinal ganglion cells: anatomy and function
- •Is glaucoma damage selective for any subgroup of RGCs?
- •Segregation
- •Isolation
- •FDT: rationale and perimetric techniques
- •SWAP: rationale and perimetric techniques
- •FDT: clinical data
- •SWAP: clinical data
- •Clinical data comparing FDT and SWAP
- •Conclusions
- •References
- •Scanning laser polarimetry and confocal scanning laser ophthalmoscopy: technical notes on their use in glaucoma
- •The GDx scanning laser polarimeter
- •Serial analysis
- •Limits
- •The Heidelberg retinal tomograph
- •Limits
- •Conclusions
- •References
- •The role of OCT in glaucoma management
- •Introduction
- •How OCT works
- •How OCT is performed
- •Evaluation of RNFL thickness
- •Evaluation of optic disc
- •OCT in glaucoma management
- •New perspective
- •Abbreviations
- •References
- •Introduction
- •Technology
- •Visual stimulation
- •Reproducibility and habituation of RFonh
- •Retinal neural activity as assessed from the electroretinogram (ERG)
- •The Parvo (P)- and Magno (M)-cellular pathways
- •Physiology
- •Magnitude and time course of RFonh in humans
- •Varying the parameters of the stimulus on RFonh
- •Luminance versus chromatic modulation
- •Frequency
- •Effect of pattern stimulation
- •Neurovascular coupling in humans
- •Clinical application
- •RFonh in OHT and glaucoma patients
- •Discussion
- •FLDF and neurovascular coupling in humans
- •Comments on clinical application of FLDF in glaucoma
- •Conclusions and futures directions
- •Acknowledgements
- •References
- •Advances in neuroimaging of the visual pathways and their use in glaucoma
- •Introduction
- •Conventional MR imaging and the visual pathways
- •Diffusion MR imaging
- •Functional MR imaging
- •Proton MR spectroscopy
- •References
- •Primary open angle glaucoma: an overview on medical therapy
- •Introduction
- •When to treat
- •Whom to treat
- •Genetics
- •Race
- •Ocular and systemic abnormalities
- •Tonometry and pachymetry
- •How to treat
- •Beta-blockers
- •Prostaglandins
- •Alpha-agonists
- •Carbonic anhydrase inhibitors (CAIs)
- •Myotics
- •Fixed combinations
- •References
- •The treatment of normal-tension glaucoma
- •Introduction
- •Epidemiology
- •Clinical features
- •Optic disk
- •Central corneal thickness
- •Disease course
- •Risk factors
- •Intraocular pressure
- •Local vascular factors
- •Immune mechanisms
- •Differential diagnosis
- •Diagnostic evaluation
- •Therapy
- •IOP reduction
- •Systemic medications
- •Neuroprotection
- •Noncompliance
- •Genetics of NTG
- •Abbreviations
- •References
- •The management of exfoliative glaucoma
- •Introduction
- •Epidemiology
- •Ocular and systemic associations
- •Ocular associations
- •Systemic associations
- •Pathogenesis of exfoliation syndrome
- •Mechanisms of glaucoma development
- •Management
- •Medical therapy
- •Laser surgery
- •Operative surgery
- •Future treatment of exfoliation syndrome and exfoliative glaucoma
- •Treatment directed at exfoliation material
- •References
- •Laser therapies for glaucoma: new frontiers
- •Background
- •Laser iridotomy
- •Indications
- •Contraindications
- •Patient preparation
- •Technique
- •Nd:YAG laser iridectomy
- •Argon laser iridectomy
- •Complications
- •LASER trabeculoplasty
- •Treatment technique
- •Mechanism of action
- •Indications for treatment
- •Contraindications to treatment
- •Patient preparation and postoperative follow-up
- •Complications of the treatment
- •Selective laser trabeculoplasty
- •Results
- •LASER iridoplasty
- •Indications
- •Contraindications
- •Treatment technique
- •Complications
- •LASER cyclophotocoagulation
- •Introduction
- •Indications and contraindications
- •Patient preparation
- •Transpupillary cyclophotocoagulation
- •Endoscopic cyclophotocoagulation
- •Transscleral cyclophotocoagulation
- •Transscleral noncontact cyclophotocoagulation
- •Transscleral contact cyclophotocoagulation
- •Complications
- •Excimer laser trabeculotomy
- •References
- •Modulation of wound healing during and after glaucoma surgery
- •The process of wound healing
- •Using surgical and anatomical principles to modify therapy
- •Growth factors
- •Cellular proliferation and vascularization
- •Cell motility, matrix contraction and synthesis
- •Drug delivery
- •Future directions: total scarring control and tissue regeneration
- •Acknowledgments
- •References
- •Surgical alternative to trabeculectomy
- •Introduction
- •Deep sclerectomy
- •Viscocanalostomy
- •Conclusions
- •References
- •Modern aqueous shunt implantation: future challenges
- •Background
- •Current shunts and factors affecting their function
- •Shunt-related factors
- •Surface area
- •Plate material
- •Valved versus non-valved
- •Commercially available devices
- •Comparative studies
- •Patient and ocular factors
- •Severity of glaucoma damage
- •Tolerance of topical ocular hypotensive medications
- •Aqueous hyposecretion
- •Previous ocular surgery
- •Scleral thinning
- •Patient cooperation for and tolerance of potential slit-lamp interventions
- •Future challenges
- •Predictability
- •Cataract formation
- •The long-term effect on the cornea
- •References
- •Model systems for experimental studies: retinal ganglion cells in culture
- •Mixed RGCs in culture
- •Retinal explants
- •Glial cultures
- •RGC-5 cells
- •Differentiation of RGC-5 cells
- •RGC-5 cell neurites
- •Advantages and disadvantages of culture models
- •References
- •Rat models for glaucoma research
- •Rat models for glaucoma research
- •Use of animal models for POAG
- •Suitability of the rat for models of optic nerve damage in POAG
- •Methods for measuring IOP in rats
- •General considerations for measuring IOP in rats
- •Assessing optic nerve and retina damage
- •Experimental methods of producing elevated IOP
- •Laser treatment of limbal tissues
- •Episcleral vein cautery
- •Conclusions
- •Abbreviations
- •Acknowledgements
- •References
- •Mouse genetic models: an ideal system for understanding glaucomatous neurodegeneration and neuroprotection
- •Introduction
- •The mouse as a model system
- •Mice are suitable models for studying IOP elevation in glaucoma
- •Tools for glaucoma research
- •Accurate IOP measurements are fundamental to the study of glaucoma
- •The future of IOP assessment
- •Assessment of RGC function
- •Mouse models of glaucoma
- •Primary open-angle glaucoma
- •MYOC
- •OPTN
- •Strategies for developing new models of POAG
- •Developmental glaucoma
- •Pigmentary glaucoma
- •Experimentally induced models of glaucoma
- •Mouse models to characterize processes involved in glaucomatous neurodegeneration
- •Similar patterns of glaucomatous damage occur in humans and mice
- •The lamina cribrosa is an important site of early glaucomatous damage
- •An insult occurs to the axons of RGCs within the lamina in glaucoma
- •What is the nature of the insult at the lamina?
- •Other changes occur in the retina in glaucoma
- •PERG and complement
- •Using mouse models to develop neuroprotective strategies
- •Somal protection
- •Axonal protection
- •Erythropoietin administration
- •Radiation-based treatment
- •References
- •Clinical trials in neuroprotection
- •Introduction
- •Methods of clinical studies
- •Issues in the design and conduct of clinical trials
- •Clinical trials of neuroprotection
- •Clinical trials of neuroprotection in ophthalmology
- •Endpoints
- •Neuroprotection and glaucoma
- •Conclusions
- •Abbreviations
- •References
- •Pathogenesis of ganglion ‘‘cell death’’ in glaucoma and neuroprotection: focus on ganglion cell axonal mitochondria
- •Introduction
- •Retinal ganglion cells and mitochondria
- •Possible causes for ganglion cell death in glaucoma
- •Mitochondrial functions and apoptosis
- •Mitochondrial function enhancement and the attenuation of ganglion cell death
- •Creatine
- •Nicotinamide
- •Epigallocatechin gallate
- •Conclusion
- •References
- •Astrocytes in glaucomatous optic neuropathy
- •Introduction
- •Quiescent astrocytes
- •Reactive astrocytes in glaucoma
- •Signal transduction in glaucomatous astrocytes
- •Protein tyrosine kinases (PTKs)
- •Serine/threonine protein mitogen-activated kinases (MAPKs)
- •G protein-coupled receptors
- •Ras superfamily of small G proteins
- •Astrocyte migration in the glaucomatous optic nerve head
- •Cell adhesion of ONH astrocytes
- •Connective tissue changes in the glaucomatous optic nerve head
- •Extracellular matrix synthesis by ONH astrocytes
- •Extracellular matrix degradation by reactive astrocytes
- •Oxidative stress in ONH astrocytes
- •Conclusions
- •Acknowledgments
- •References
- •Glaucoma as a neuropathy amenable to neuroprotection and immune manipulation
- •Glaucoma as a neurodegenerative disease
- •Oxidative stress and free radicals
- •Excessive glutamate, increased calcium levels, and excitotoxicity
- •Deprivation of neurotrophins and growth factors
- •Abnormal accumulation of proteins
- •Pharmacological neuroprotection for glaucoma
- •Protection of the retinal ganglion cells involves the immune system
- •Searching for an antigen for potential glaucoma therapy
- •Concluding remarks
- •References
- •Oxidative stress and glaucoma: injury in the anterior segment of the eye
- •Introduction
- •Oxidative stress
- •Trabecular meshwork
- •IOP increase and free radicals
- •Glaucomatous cascade
- •Nitric oxide and endothelins
- •Extracellular matrix
- •Metalloproteinases
- •Other factors of interest
- •Therapeutic and preventive substances of interest in glaucoma
- •Ginkgo biloba extract
- •Green tea
- •Ginseng
- •Memantine and its derivates
- •Conclusions
- •Abbreviations
- •References
- •Conclusions on neuroprotective treatment targets in glaucoma
- •Acknowledgments
- •References
- •Involvement of the Bcl2 gene family in the signaling and control of retinal ganglion cell death
- •Introduction
- •Intrinsic apoptosis vs. extrinsic apoptosis
- •The Bcl2 family of proteins
- •The requirement of BAX for RGC soma death
- •BH3-only proteins and the early signaling of ganglion cell apoptosis
- •Conclusion
- •Abbreviations
- •Acknowledgments
- •References
- •Assessment of neuroprotection in the retina with DARC
- •Introduction
- •DARC
- •Introducing the DARC technique
- •Annexin 5-labeled apoptosis and ophthalmoloscopy
- •Detection of RGC apoptosis in glaucoma-related animal models with DARC
- •Assessment of glutamate modulation with DARC
- •Glutamate at synaptic endings
- •Glutamate excitotoxicity in glaucoma
- •Assessment of coenzyme Q10 in glaucoma-related models with DARC
- •Summary
- •Abbreviations
- •Acknowledgment
- •References
- •Potential roles of (endo)cannabinoids in the treatment of glaucoma: from intraocular pressure control to neuroprotection
- •Introduction
- •The endocannabinoid system in the eye
- •The IOP-lowering effects of endocannabinoids
- •Endocannabinoids and neuroprotection
- •Conclusions
- •References
- •Glaucoma of the brain: a disease model for the study of transsynaptic neural degeneration
- •Retinal ganglion cells, retino-geniculate neurons
- •Lateral geniculate nucleus
- •Mechanisms of RGC injury in glaucoma
- •Transsynaptic degeneration of the lateral geniculate nucleus in glaucoma
- •Neural degeneration in magno-, parvo-, and koniocellular LGN layers
- •Visual cortex in glaucoma
- •Neuropathology of glaucoma in the visual pathways in the human brain
- •Mechanisms of glaucoma damage in the central visual pathways
- •Implications of central visual system injury in glaucoma
- •Conclusion
- •Acknowledgments
- •References
- •Clinical relevance of optic neuropathy
- •Is there a remodeling of retinal circuitry?
- •Behavioral consequences of glaucoma
- •Glaucoma as a neurodegenerative disease versus neuroplasticity and adaptive changes
- •Future directions
- •Acknowledgment
- •References
- •Targeting excitotoxic/free radical signaling pathways for therapeutic intervention in glaucoma
- •Introduction
- •Channel properties of NMDA receptors correlated with excitotoxicity
- •Downstream signaling cascades after overactivation of NMDA receptors
- •Relevance of excitotoxicity to glaucoma
- •Therapeutic approaches to prevent RGC death by targeting the pathways involved in NMDA excitotoxicity
- •Drugs targeting NMDA receptors
- •Kinetics of NMDA receptor antagonists
- •Memantine
- •NitroMemantines
- •Drugs targeting downstream signaling molecules in NMDA-induced cell death pathways
- •p38 MAPK inhibitors
- •Averting caspase-mediated neurodegeneration
- •Abbreviations
- •Acknowledgments
- •References
- •Stem cells for neuroprotection in glaucoma
- •Introduction
- •Glaucoma as a model of neurodegenerative disease
- •Why use stem cells for neuroprotective therapy?
- •Stem cell sources
- •Neuroprotection by transplanted stem cells
- •Endogenous stem cells
- •Key challenges
- •Conclusion
- •Abbreviations
- •Acknowledgments
- •References
- •The relationship between neurotrophic factors and CaMKII in the death and survival of retinal ganglion cells
- •Introduction
- •Glaucoma and the RGCs
- •Are other retinal cells affected in glaucoma?
- •Retinal ischemia related glaucoma
- •Excitotoxicity and the retina
- •Signal transduction
- •NMDA receptor antagonists and CaMKII
- •Caspase-3 activation in NMDA-induced retinal cell death and its inhibition by m-AIP
- •BDNF and neuroprotection of RGCs
- •Summary and conclusions
- •Abbreviations
- •Acknowledgments
- •References
- •Evidence of the neuroprotective role of citicoline in glaucoma patients
- •Introduction
- •Patients: selection and recruitment criteria
- •Pharmacological treatment protocol
- •Methodology of visual function evaluation: electrophysiological examinations
- •PERG recordings
- •VEP recordings
- •Statistic evaluation of electrophysiological results
- •Electrophysiological (PERG and VEP) responses in OAG patients after the second period of evaluation
- •Effects of citicoline on retinal function in glaucoma patients: neurophysiological implications
- •Effects of citicoline on neural conduction along the visual pathways in glaucoma patients: neurophysiological implications
- •Possibility of neuroprotective role of citicoline in glaucoma patients
- •Conclusive remarks
- •Abbreviations
- •References
- •Neuroprotection: VEGF, IL-6, and clusterin: the dark side of the moon
- •Neuroprotection: VEGF-A, a shared growth factor
- •VEGF-A isoforms
- •VEGF-A receptors
- •Angiogenesis, mitogenesis, and endothelial survival
- •Neurotrophic and neuroprotective effect
- •Intravitreal VEGF inhibition therapy and neuroretina toxicity
- •Neuroprotection: clusterin, a multifunctional protein
- •Clusterin/ApoJ: a debated physiological role
- •Clusterin and diseases
- •Clusterin and the nervous system
- •Neuroprotection: IL-6, VEGF, clusterin, and glaucoma
- •Rational basis for the development of coenzyme Q10 as a neurotherapeutic agent for retinal protection
- •Introduction
- •Ischemia model
- •Neuroprotective effect of Coenzyme Q10 against cell loss yielded by transient ischemia in the RGC layer
- •Retinal ischemia and glutamate
- •Coenzyme Q10 minimizes glutamate increase induced by ischemia/reperfusion
- •Summary
- •Acknowledgment
- •References
- •17beta-Estradiol prevents retinal ganglion cell loss induced by acute rise of intraocular pressure in rat
- •Methods
- •Morphometric analysis
- •Microdialysis
- •Drug application
- •Statistical analysis
- •Results
- •17beta-Estradiol pretreatment minimizes RGC loss
- •Discussion
- •Acknowledgment
208
NTG as a component of damage, or in a subset of susceptible patients. A goal of current glaucoma research is to develop neuroprotective treatment strategies to prevent retinal ganglion cell death (Kuehn et al., 2005). Memantine is a promising new drug that is currently being investigated for treatment of POAG. Memantine is thought to protect the optic nerve from the toxic glutamate levels that may lead to apoptosis of retinal ganglion cells in glaucoma. Any new treatment regime should have a rational scientific basis, be delivered safely to the site of damage, and show both efficacy and safety through randomized prospective clinical trials. Since glaucoma is a slowly progressive disease, it can take many years to detect a significant benefit of new treatments, particularly when added to robust IOP-lowering treatments.
Noncompliance
Noncompliance may be an important reason that some glaucoma suspects or glaucoma patients under ‘‘treatment’’ go on to develop severe deterioration of vision. Many of these individuals may have retained meaningful vision if appropriate therapy had been effectively applied. Several studies have evaluated factors that predispose glaucoma patients to noncompliance. Low socioeconomic status, language barrier, and aspects of treatment regime (i.e., dose frequency, number of medications, number of clinic visits) have all been linked to noncompliance. Few studies have been conducted to look at factors for noncompliance in the NTG population specifically. One study showed that approximately 50% of patients classified as NTG suspects lacked appropriate follow-up care. The lack of health insurance was a significant barrier for these patients in this study (Ngan et al., 2007). Another study showed that even within a single comprehensive insurance plan patients thought to require treatment for glaucoma were not being monitored at recommended intervals set by medical guidelines (Friedman et al., 2005). The Glaucoma Adherence and Persistency Study has shown that patient adherence to glaucoma medications is poor and comparable to other chronic diseases (Friedman et al., 2007).
More research is needed to better identify individuals at greatest risk for noncompliance. The Patient Care Improvement Project conducted by
the American Glaucoma Society is attempting to identify both the barriers to compliance and tools to overcome these obstacles (American Glaucoma Society). This project has suggested that tools such as memory aids and tracking tools for medications, appointment reminders, and a new bottle design that would alert patients that it is time to refill medications may prove to be helpful. Also, social programs that empower the patient like support groups and accessible patient education classes would be helpful. As the glaucoma population grows, it will become very important that we address the problem of noncompliance. This significant issue will become an even larger burden on society as it takes people out of the work force and makes them dependent on social programs.
Genetics of NTG
A great deal of ongoing research is dedicated to identifying a genetic basis for NTG. An OPA1 gene polymorphism (OPA1 IVS 8+32 T/C) has been associated with NTG, and one study showed that it may be used as a marker for this disease association (Mabuchi et al., 2007). Little is known, however, about the function of the OPA1 protein and how this polymorphism may cause glaucomatous neuropathy. An optineurin sequence variation, Glu50Lys OPTN, has been associated with familial NTG (Alward et al., 2003). This change, however, is responsible for less than 0.1% of open-angle glaucomas. It is unclear exactly what the function of this novel gene is. It is thought to protect the optic nerve from TNF-a-mediated apoptosis, and consequently a loss of function of this protein may decrease the threshold for ganglion cell apoptosis. Also, studies of lymphocytes in NTG have shown altered expression of the p53 gene, which is a known regulator of apoptosis (Wiggs, 2005). These results indicate that abnormal regulation of retinal ganglion cell apoptosis may be one of the IOPindependent mechanisms of optic nerve damage in glaucoma. It is unlikely that a single gene or even a small set of genes will be accountable for the clinical disease. It is likely that downstream effects, including but not limited to proteonomics, play a significant role in mechanisms of damage.
These require further intensive investigation to unravel and are likely to be quite complex.
Abbreviations |
|
ACE |
angiotensin-converting enzyme |
CCT |
central corneal thickness |
CNTGS |
Collaborative Normal-Tension |
|
Glaucoma Study |
IOP |
intraocular pressure |
NTG |
normal-tension glaucoma |
POAG |
primary open-angle glaucoma |
References
AGIS (Advanced Glaucoma Intervention Study) Investigators. (2001) The advanced glaucoma intervention study: 8. Risk of cataract formation after trabeculectomy. Arch. Ophthalmol., 119(12): 1771–1779.
Allingham, R.R., Damji, K., Freedman, S., Moroi, S., Shafranov, G. and Shields, M.B. (2005) Chronic open-angle glaucoma and normal-tension glaucoma. In: Pine J. and Murphy J. (Eds.), Shields’ Textbook of Glaucoma (5th edition). Lippincott Williams & Wilkins, Philadelphia, PA, pp 197–207. Chapter 11.
Alward, W., Kwon, Y., Kawase, K., Craig, J., Hayreh, S., Johnson, A., Khanna, C., Yamamoto, T., Mackey, D., Roos, B., Affatigato, L., Sheffield, V. and Stone, E. (2003) Evaluation of optineurin sequence variations in 1,048 patients with open-angle glaucoma. Am. J. Ophthalmol., 136: 904–910.
American Glaucoma Society. Patient Care Improvent Project: Pearls to Improve Patient Compliance. http://www. glaucomaweb.org/associations/5224/files/02Booklet_Pearls.F.pdf Bose, S., Piltz, J.R. and Brenton, M.E. (1995) Nimodipine, a centrally active calcium antagonist, exerts a beneficial effect on contrast sensitivity in patients with NTG and in control
subjects. Ophthalmology, 102(8): 1236–1241.
Butt, Z., McKillop, G., O’Brien, C., Allan, P. and Aspinall, P. (1995) Measurement of ocular blood flow velocity using color Doppler imaging in low tension glaucoma. Eye, 9(Pt 1): 29–33.
Caprioli, J. (1998) The treatment of normal-tension glaucoma. Am. J. Ophthalmol., 126(4): 578–581.
Caprioli, J. and Spaeth, G.L. (1984) Comparison of visual field defects in the low-tension glaucomas with those in the hightension glaucomas. Am. J. Ophthalmol., 97: 730–737.
Caprioli, J. and Spaeth, G.L. (1985) Comparison of the optic nerve head in highand low-tension glaucoma. Arch. Ophthalmol., 130: 1145–1149.
Cartwright, N.J. and Anderson, D.R. (1988) Correlation of asymmetric damage with asymmetric intraocular pressure in NTG (low tension glaucoma). Arch. Ophthalmol., 106: 898–900.
Cartwright, M.J., Grajewski, A.L., Friedberg, M.L., Anderson, D.R. and Richards, D.W. (1992) Immune-related disease
209
and normal-tension glaucoma: a case–control study. Arch. Ophthalmol., 110(4): 500–502.
Crichton, A., Drance, S.M., Douglas, G.R. and Schulzer, M. (1989) Unequal intraocular pressure and its relation to asymmetric visual field defects in low-tension glaucoma. Ophthalmology, 96: 1312–1314.
Cursiefen, C., Wisse, M., Cursiefen, S., Junemann, A., Martus, P. and Korth, M. (2000) Migraine and tension headache in high-pressure and normal-pressure glaucoma. Am. J. Ophthalmol., 129: 102–104.
Drance, S., Anderson, D.R. and Schulzer, M. (2001) Risk factors for progression of visual field abnormalities in normal-tension glaucoma. Am. J. Ophthalmol., 131: 699–708.
Friedman, D.S., Nordstrom, B., Mozaffari, E. and Quigley, H.A. (2005) Glaucoma management among individuals enrolled in a single comprehensive insurance plan. Ophthalmology, 112: 1500–1504.
Friedman, D.S., Quigley, H.A., Gelb, L., Tan, J., Margolis, J., Shah, S.N., Kim, E.E., Zimmerman, T. and Hahn, S.R. (2007) Using pharmacy claims data to study adherence to glaucoma medications: methodology and findings of the Glaucoma Adherence and Persistency Study (GAPS). Invest. Ophthalmol. Vis. Sci., 48: 5052–5057.
Gaasterland, D.E., Allingham, R.R., Gross, R.L., Jampel, H.D., Kwon, Y.H., Prum, B.E. and Gordon, M.O. (2005) In: Garratt S. (Ed.), American Academy of Ophthalmology. Primary Open-Angle Glaucoma, Preferred Practice Pattern. San Francisco, American Academy of Ophthalmology, pp. 1–23. Available at www.aao.org/ppp
Geijssen, H.C. (1991) Studies on Normal-Pressure Glaucoma. Kugler, Amstelveen, The Netherlands.
Graefe, A.V. (1857) Uber die Iridectomie bei Glaucoma und u¨ber den Glaucomato¨sen Prezess. Albrecht von Graefes Archiv. Klin. Exp. Ophthalmol., 13: 456–650.
Greenfield, D.S., Liebmann J.M., Ritch, R., Krupin, T. and Low-Pressure Glaucoma Study Group. (2007) Visual field and intraocular pressure asymmetry in the Low-Pressure Glaucoma Treatment Study. Ophthalmology, 114(3): 460–465.
Greenfield, D.S., Siatkowski, R.M., Glaser, J.S., Schatz, N.J. and Parrish, R.K. (1998) The cupped disc: who needs neuroimaging? Ophthalmology, 105: 1866–1874.
Harrington, D.E. (1969) The pathogenesis of the glaucoma field: clinical evidence that circulatory insufficiency in the optic nerve is the primary cause of visual field in glaucoma. Am. J. Ophthalmol., 47(2): 177–185.
Harris, A., Rechtman, E., Siesky, B., Jonescu-Cuypers, C., McCranor, L. and Garzozi, H.J. (2005) The role of optic nerve blood flow in the pathogenesis of glaucoma. Ophthalmol. Clin. North Am., 18(3): 345–353.
Hayreh, S.S., Podhajsky, P. and Zimmerman, M.B. (1999) Beta-blocker eye drops and nocturnal arterial hypertension. Am. J. Ophthalmol., 128(3): 301–309.
Hayreh, S.S., Zimmerman, M.B., Podhajsky, P. and Alward, W.L. (1994) Nocturnal arterial hypotension and its role in optic nerve head and ocular ischemic disorders. Am. J. Ophthalmol., 117(5): 603–624.
Hirooka, K., Baba, T., Fujimura, T. and Shiraga, F. (2006) Prevention of visual field defect progression with
210
angiotensin-converting enzyme inhibitor in eyes with normaltension glaucoma. Am. J. Ophthalmol., 142: 523–524.
Kawano, J., Tomidokoro, A., Mayama, C., Kunimatsu, S., Tomita, G. and Araie, M. (2006) Correlation between hemifield visual field damage and corresponding parapapillary atrophy in normal-tension glaucoma. Am. J. Ophthalmol., 142: 40–45.
Kim, D.M., Hwang, U.S., Park, K.H. and Kim, S.H. (2005) Retinal nerve fiber layer thickness in the fellow eyes of normal-tension glaucoma patients with unilateral visual field defect. Am. J. Ophthalmol., 140: 165–166.
Kitazawa, Y., Shirai, H. and Go, F.J. (1989) The effect of Ca2+-antagonist on visual field in low-tension glaucoma. Graefes Arch. Clin. Exp. Ophthalmol., 227(5): 408–412.
Krupin, T., Liebmann, J.M., Greenfield, D.S., Rosenberg, L.F., Ritch, R. and Yang, J.W. (2005) The low-pressure glaucoma treatment study: study design and baseline characteristics of enrolled patients. Ophthalmology, 112(3): 376–385.
Kuehn, M., Fingert, J. and Kwon, Y. (2005) Retinal ganglion cell death in glaucoma: mechanisms and neuroprotective strategies. Ophthalmol. Clin. North Am., 18: 383–395.
Lumme, P., Tuulonen, A., Airaksinen, P.J. and Alanko, H.I. (1991) Neuroretinal rim area in low tension glaucoma: effect of nifedipine and acetazolamide compared to no treatment. Acta Ophthalmol. (Copenh.), 69(3): 293–298.
Mabuchi, F., Tang, S., Kashiwagi, K., Yamagata, Z., Iijima, H. and Tsukahara, S. (2007) The OPA1 gene polymorphism is associated with normal tension and high tension glaucoma. Am. J. Ophthalmol., 143: 125–130.
Martus, P., Stroux, A., Budde, S., Mardin, C., Korth, M. and Jonas, J. (2005) Predictive factors for progressive optic nerve damage in various types of chronic open-angle glaucoma. Am. J. Ophthalmol., 139: 999–1009.
Melamed, S., Levkovitch-Verbin, H., Krupsky, S. and Treister, G. (1998) Confocal tomographic angiography of the optic nerve head in patients with glaucoma. Am. J. Ophthalmol., 125(4): 447–456.
Meyer, J.H., Brandi-Dohrn, J. and Funk, J. (1996) Twenty four hour blood pressure monitoring in normal tension glaucoma. Br. J. Ophthalmol., 80(10): 864–867.
Morad, Y., Sharon, E., Hefetz, L. and Nemet, P. (1998) Corneal thickness and curvature in normal-tension glaucoma. Am. J. Ophthalmol., 125: 164–168.
Netland, P.A., Grosskreutz, C.L., Feke, G.T. and Hart, L.J. (1995) Color Doppler ultrasound analysis of ocular circulation after topical calcium channel blocker. Am. J. Ophthalmol., 119(6): 694–700.
Ngan, R., Lam, D.L., Mudumbai, R.C. and Chen, P.P. (2007) Risk factors for noncompliance with follow-up among normal-tension glaucoma suspects. Am. J. Ophthalmol., 144(2): 310–311.
Nicolela, M.T., Buckley, A.R., Walman, B.E. and Drance, S.M. (1996) A comparative study of the effects of timolol and latanoprost on blood flow velocity of the retrobulbar vessels. Am. J. Ophthalmol., 122: 784–789.
Oguri, A., Sogano, S., Yamamoto, T. and Kitazawa, Y. (1998) Incidence of elevation of intraocular pressure over time and associated factors in normal tension glaucoma. J. Glaucoma, 7(2): 117–120.
Ong, K., Farinelli, A., Billson, F., Houang, M. and Stern, M. (1995) Comparative study of brain magnetic resonance imaging findings in patients with low-tension glaucoma and control subjects. Ophthalmology, 102(11): 1632–1638.
Phelps, C.D. and Corbett, J.J. (1985) Migraine and low-tension glaucoma: a case-control study. Invest. Ophthalmol. Vis. Sci., 26: 1105–1108.
Quigley, H.A., Nickells, R.W., Kerrigan, L.A., Pease, M.E., Thibault, D.J. and Zack, D.J. (1995) Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest. Ophthalmol. Vis. Sci., 36(5): 774–786.
Rojanapongpun, P., Drance, S.M. and Morrison, B.J. (1993) Ophthalmic artery flow velocity in glaucomatous and normal subjects. Br. J. Ophthalmol., 77: 25–29.
Romano, C., Barrett, D.A., Li, Z., Pestronk, A. and Wax, M.B. (1995) Anti-rhodopsin antibodies in sera from patients with normal-pressure glaucoma. Invest. Ophthalmol. Vis. Sci., 36(10): 1968–1975.
Schumann, J., Orgul, S., Gugleta, K., Dubler, B. and Flammer, J. (2000) Interocular difference in progression of glaucoma correlates with interocular differences in retrobulbar circulation. Am. J. Ophthalmol., 129(6): 728–733.
Shiose, Y., Kitazawa, Y., Tsukahara, S., Akamatsu, T., Mizokami, K., Futa, R., Katsushima, H. and Kosaki, H. (1991) Epidemiology of glaucoma in Japan: a nationwide glaucoma survey. Jpn. J. Ophthalmol., 35(2): 133–155.
Simmons, S.T., Coiffi, G.A., Gross, R.L., Myers, J.S., Netland, P.A., Samples, J.R., Wright, M.M. and Brown, S.V. (2004) Open-Angle Glaucoma. In: Simmons S.T. (Ed.), American Academy of Ophthalmology, Basic and Clinical Science Course: Glaucoma, Section 10, Chapter 4. American Academy of Ophthalmology, USA, pp. 92–96.
Stroman, G.A., Stewart, W.C., Golnik, K.C., Cure, J.K. and Olinger, R.E. (1995) Magnetic resonance imaging in patients with low-tension glaucoma. Arch. Ophthalmol., 113(2): 168–172.
The Collaborative Normal-Tension Glaucoma Study (CNTGS). (1998a) Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. The Collaborative Normal-Tension Glaucoma Study Group. Am. J. Ophthalmol., 126: 487–497.
The Collaborative Normal-Tension Glaucoma Study (CNTGS). (1998b) The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. The Collaborative Normal-Tension Glaucoma Study Group. Am. J. Ophthalmol., 126: 498–505.
Waldmann, E., Gasser, P., Dubler, B., Huber, C. and Flammer, J. (1996) Silent myocardial ischemia in glaucoma and cataract patients. Graefes Arch. Clin. Exp. Ophthalmol., 234(10): 595–598.
Wax, M.B., Barrett, D.A. and Pestronk, A. (1994) Increased incidence of paraproteinemia and autoantibodies in patients with normal-pressure glaucoma. Am. J. Ophthalmol., 117(5): 561–568.
Wiggs, J.L. (2005) Genes associated with human glaucoma. Ophthalmol. Clin. North Am., 18(3): 335–343.
Woo, S., Park, K. and Kim, D. (2003) Comparison of localised nerve fibre layer defects in normal tension glaucoma and primary open angle glaucoma. Br. J. Ophthalmol., 87: 695–698.