- •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
114
Fig. 3. (Continued).
size (Eisner et al., 2006), and a flaw-normative database that did not rule out, at least, the cases with a major learning effect. SITA SWAP, a novel program included in the latest version of the HFA II-i, has a shorter duration (between 3 and 6 min) and may at least partially reduce the impact of such limitations (Bengtsson and Heijl, 2003, 2006) and improve the performances of this perimetry.
Clinical data comparing FDT and SWAP
The studies comparing the diagnostic efficacy of FDT and SWAP are the most pertinent to the purpose of this review, but, to the best of our knowledge, only 10 have been published. Ideally, each study should answer to two questions: ‘‘Is it worth testing patients with glaucoma or glaucoma suspect with unconventional perimetries?’’ and
‘‘Which one, among FDT and SWAP, is preferable?’’ The first question implies a longitudinal design to verify whether unconventional perimetries are more effective than SAP in detecting conversion to the disease or progression. As funding allocation is common for all perimetries, in the case of their validation, unconventional perimetries would be performed at the expense of SAP. This hypothetical superiority over SAP should therefore be demonstrated using an independent ‘‘gold standard’’ for diagnosis (ONH or RNFL appearance). Unfortunately, as shown in Table 3, no studies fulfilled all these features, and therefore any conclusion on the efficacy of unconventional perimetries over SAP must be considered with great caution.
Landers conducted a study over 62 OH patients (normal ONH and SAP) to verify whether FDT and SWAP could detect underlying earlier visual field loss (Landers et al., 2003). Patients underwent SAP, SWAP, and FDT every year for a 3-year follow-up. At the end of the study, nine subjects had abnormal SWAP and 10 abnormal FDT. Field loss at SAP developed in five subjects, all of whom had pre-existing abnormal SWAP and FDT results; no SAP defects developed in patients with normal SWAP or FDT. This study suggested that both FDT and SWAP are useful tools to predict the development of SAP loss in OH patients.
A number of cross-sectional studies obtained similar results, thus suggesting that FDT and SWAP were equally effective in diagnosing pre-perimetric glaucoma cases (Bayer and Erb,
115
2002; Bayer et al., 2002; Leeprechanon et al., 2007), with a sensitivity ranging from 20 (Ferreras et al., 2007) to 72% (Leeprechanon et al, 2007) for FDT, and from 20 (Ferreras et al., 2007) to 54% (Leeprechanon et al., 2007) for SWAP; specificity was similar for the two techniques (53% for FDT vs. 44% for SWAP) (Leeprechanon et al., 2007).
Other studies suggested that FDT may achieve better diagnostic performances than SWAP (Bowd et al., 2001; Soliman et al., 2002). An interesting study compared the diagnostic ability of several morphological and functional tests in diagnosing early glaucoma (Bowd et al., 2001). Two different definitions were adopted, based on ONH appearance and SAP. The area under the curve (AUC) was calculated for each test; overall, FDT had better diagnostic power than SWAP (AUCs of 0.87 and 0.88 compared to 0.76 and 0.78 for SWAP).
Another relevant piece of information from this study was that, when specificity was set at 90%, the two techniques obtained a poor diagnostic agreement. This means that, at the initial stage of the disease, no single perimetric test was always affected, whereas the other remained normal, a fact that has been recently confirmed (Sample et al., 2006).
On the other hand, performing a battery of SWAP and FDT is a good strategy for identifying the largest number of early glaucoma cases as possible (Ferreras et al., 2007; Horn et al., 2007).
Detection of early glaucoma cases can be further maximized in both screening (To´th et al., 2007)
Table 3. Characteristics of the design of the studies comparing FDT and SWAP available in literature
|
Cross-sectional |
Longitudinal (follow-up) |
Gold standard |
|
|
Which is better? |
|
|
|
|
|
|
|
|
|
|
SAP only SAP+ONH |
ONH only |
|
|
|
|
|
|
|
|
|
Bowd et al., 2001 |
X |
|
X |
X |
FDT |
|
Bayer et al., 2002 |
X |
|
X |
|
|
FDT ¼ SWAP |
Soliman et al., 2002 |
X |
|
X |
|
|
FDT |
Landers et al., 2003 |
|
X (36 months) |
X |
|
|
FDT ¼ SWAP |
Bagga et al., 2006 |
X |
|
X |
|
|
FDT ¼ SWAP |
Sample et al., 2006 |
X |
|
|
X |
FDT |
|
Shah, 2007 |
X |
|
X |
X |
FDT |
|
Ferreras et al., 2007 |
X |
|
X |
|
|
FDT ¼ SWAP |
Horn et al., 2007 |
X |
|
X |
|
|
FDT ¼ SWAP |
Leeprechanon et al., 2007 |
X |
|
X |
|
|
FDT ¼ SWAP |
116
and specialistic (Horn et al., 2003; Bagga et al., 2006) settings if a combination of functional and morphological examinations is obtained. It has been shown that adding FDT perimetry to each of
Table 4. Items that are required to improve the clinical applicability of unconventional perimetries
1.Provide high-quality scientific evidence of the importance of increasing the frequency and the regularity of visual test repetitions (with both conventional and, eventually, unconventional techniques) in order to obtain a more generous resource allocation for perimetry in glaucoma management
2.Provide high-quality scientific evidence of the superiority, if any, of unconventional perimetries in the early diagnosis of glaucoma:
-Prospective, longitudinal studies
-Possibly multicentric studies
-Morphological ‘‘gold standard’’
-Comparative data between conventional and unconventional techniques
-Large sample size to provide a reasonably high number of progressing cases
3.Unify and validate the diagnostic criteria for FDT and SWAP
4.As for SAP, generate software to evaluate FDT and SWAP progression
5.Validate the new SITA SWAP program
the best structural parameters led to a significant increase in sensitivity without a significant change in specificity compared with structural parameters alone, whereas adding SWAP to each of the best structural parameters led to a significant increase in sensitivity and a significant decrease in specificity compared with each structural parameter alone (Shah et al., 2007).
Conclusions
FDT and SWAP are two relatively novel perimetric techniques that can provide additional or confirmatory evidence in glaucoma patients. Furthermore, other perimetric techniques (MAP and HPRP) may have a role in the management of the disease, but due to their poor diffusion their use is still limited to experimental settings.
Some functional features of the RGCs, such as segregation (Kaplan, 2004; Callaway, 2005), isolation (Sample et al., 1996), and redundancy (Johnson, 1994; Haymes et al., 2005), have been only recently clarified; these aspects provided confirmation that both SWAP and FDT, thanks
Fig. 4. The case of a 71-year-old man showing RNFL defects (a), normal SAP (b), and FDT (c) and full-threshold SWAP (d) abnormalities at baseline who developed glaucomatous SAP defects after 7 years (e).
117
Fig. 4. (Continued).
to their selective evaluation of subgroups of RGCs with low number and redundancy, actually investigate functions that are impaired in the early stages of the disease (Johnson et al., 1993a, b; Trible et al., 2000; Landers et al., 2003).
Clinical studies on SWAP and FDT are growing in number, and they seem to confirm the ability of both techniques in detecting abnormalities in early
glaucoma cases otherwise judged as normal on the basis of SAP results (the so-called ‘‘pre-perimetric’’ glaucomas) (Johnson et al., 1993a, b; Johnson and Samuels, 1997). Overall, FDT shows a slightly better diagnostic power, a more solid database (with lower intraand inter-individual variability), and more reliable results than SWAP (Soliman et al., 2002; Zangwil et al., 2006).
118
Fig. 4. (Continued).
On the other side, the clinical applicability of both procedures is still limited by a number of factors. Serious doubts on the validity of the full-threshold SWAP database have been raised (high intraand intertest variability; presence of a learning effect also in patients already experienced with SAP) (Bengtsson and Heijl, 2003; Rossetti et al., 2006), whereas no data derived from clinical settings are currently available for the novel SITA SWAP program.
The testing strategy for SWAP is very similar to SAP, and therefore the same diagnostic criteria
could be used to detect glaucoma changes (although some authors raised skepticism on the validity of SAP criteria for SWAP) (Johnson et al., 2002). On the other side, several criteria to define FDT abnormality have been proposed (Delgado et al., 2002), but no criterion has been clearly validated and accepted. As for all physical measurements, also for first-generation FDT, it has been shown that the loosest criterion (i.e., abnormality defined in the presence of at least one location with Po5%) obtains the highest sensitivity but it
119
Fig. 4. (Continued).
invariably causes an increase of the false-positive rate. The novel Matrix FDT uses a testing program that is more similar to SAP; this could also probably allow the introduction of more uniform criteria for abnormality for this technique.
The large part of the literature on SWAP and FDT is composed of cross-sectional studies; very
few prospective data are available, and they were conducted on small groups of patients. Many studies had a selection bias, since only patients with normal SAP were recruited; as a consequence, the diagnostic power of SAP may be underestimated, a fact that has been confirmed by the recent studies considering the appearance of ONH
120
Fig. 4. (Continued).
as the ‘‘gold standard’’ for diagnosis (Bagga et al., 2006; Sample et al., 2006). Finally, very scanty data are available on the efficacy of SWAP and FDT in detecting the progression of glaucoma.
Being resource allocation common to all perimetries, in routine clinical practice the use of unconventional perimetries is strictly related to a reduction in the number of SAP tests. Unfortunately, the number of SAP examinations already
falls substantially below published recommendations for maintaining minimum practice standards in the majority of clinical settings (Friedman et al., 2005). Based on the actual knowledge of unconventional perimetry, a further reduction seems inappropriate, above all in consideration that SAP provides the only parameters having a direct relevance to quality-of-life measures (Gutierrez et al., 1997; Parrish et al., 1997; Sherwood et al.,
