although diagnosis of moderate to severe cases of glaucoma is relatively straightforward , with diagnoses confirmed based on the presence of typical visual field ( vf ) defects on standard automated perimetry ( sap ) and corresponding signs of glaucomatous onh damage , the disease typically remains asymptomatic in the early stages .
standard automated perimetry has been widely used for diagnosis , staging , and monitoring of glaucoma , but is only likely to detect functional deficits after at least 20%40% of rgcs have been lost . furthermore , visual field testing is often variable , and diagnosis may require repeated testing .
identification of early glaucomatous structural damage , such as structural remodeling of the onh and inner retinal layers , is essential for early diagnosis , management , and prevention of vision loss .
clinical assessment using multiple parameters , including peripapillary rnfl , onh , and macular parameters , has proven useful , not only for management and diagnosing glaucoma at various levels of severity , but for evaluating risk in glaucoma suspects . although the use of multiple parameters could increase false - positive results
, structural damage may be present in one parameter and not the other , and thus it is helpful to have information from the macula , onh , and rnfl in glaucoma diagnosis .
current sd - oct rnfl thickness parameters alone , however , have good diagnostic accuracy and help clinicians in determining severity stages and differentiating normal from glaucomatous eyes in the early stages .
retinal nerve fiber layer parameters most extensively researched include : global average circumpapillary rnfl thickness ( average of thickness measurements in the circumpapillary circle centered on the onh ) , thickness deviation map , and thickness parameters measured by quadrants or clock - hour sectors .
in general , average circumpapillary rnfl thickness and inferior sector rnfl thicknesses are the oct parameters with the best diagnostic accuracy , with superior quadrant thickness values following in terms of sensitivity
. this agrees with prior studies showing superior and inferior areas of the optic nerve most commonly affected glaucoma ( fig .
the diagnostic accuracy of ss - oct circumpapillary rnfl parameters are similar to those of sd - oct . for detection of glaucomatous damage ,
the sd - oct rnfl parameters have sensitivities ranging from 60% to 98% and specificities ranging from 80% to 95% .
diagnostic performance decreases , however , for detection of early disease to 48% to 77% at the same specificity range for patients with minimal visual field losses .
recent evidence shows , however , that even before the appearance of any vf defects on sap , rnfl average thickness parameters could detect glaucomatous damage : at 95% specificity , up to 35% of eyes had abnormal thickness values 4 years prior to detectable vf loss and 19% had abnormal values 8 years prior .
the reproducibility of current sd - oct rnfl thickness parameters is excellent , with global average rnfl thickness generally being the most reproducible .
retinal nerve fiber layer analysis from spectralis - oct ( heidelberg engineering , heidelberg , germany ) demonstrating glaucomatous damage .
the rnfl evaluation in the right eye ( od ) shows abnormalities in the superior and inferior quadrants .
evaluation of the macular region is also important in glaucoma diagnosis ; and oct has become an attractive means for identifying glaucomatous macular damage .
glaucomatous damage of the macula is difficult to detect and generally overlooked or underestimated by clinicians when using the most common automated perimetry testing : 24 - 2 ( 6 grid ) vf test .
macular damage occurs early in the disease process and can take the form of arcuate defects , diffuse , widespread damage , and/or local damage , or some combination of these . in eyes without other macular pathology , there is less variability and a lower likelihood of the presence of anomalous structural characteristics in the macula compared with the optic disc and peripapillary region .
assessment of the macula may also avoid some limitations of circumpapillary measurements , such as interference from retinal and optic nerve head vasculature , peripapillary atrophy , and variable placement of the measurement circle around the disc .
structures that thin and diminish in glaucoma comprise a large proportion of total macular thickness ; these include rnfl and rgcs , but also inner plexiform layer .
the rgc layer is thickest in the perimacular region , and its thinning is likely responsible for the decreased total macular thickness observed in glaucomatous eyes .
preservation of central vision until late in the disease may suggest macular assessment is not useful for glaucoma detection .
the macular rgc layer , however , is up to seven cells thick and contains more than 50% of the eye 's rgcs , and structural changes in the macula can thus easily precede detectable vf losses .
additionally , changes in this layer are more likely be the result of pathologic change rather than normal variation , and thus measurements of this layer could potentially be more sensitive than rnfl thickness parameters .
segmentation of the ganglion cell layer alone , however , remains very difficult due to low reflectivity .
advances in oct have allowed for better quantitative evaluation of macular rgc damage and have enabled more detailed segmentation of the macular inner retinal layers and the entire macular thickness .
although some studies show that macular rnfl ( mrnfl ) thickness in sd - oct is less accurate than circumpapillary rnfl in glaucoma diagnosis or detecting preperimetric glaucoma , novel segmentation algorithms have increased the diagnostic utility of macular evaluation .
parameters , such as mrnfl , ganglion cell layer with inner plexiform layer ( cgipl ) , and the ganglion cell complex ( gcc ) , which includes mrnfl , ganglion cell layer , and inner plexiform layer , can distinguish glaucomatous eyes from those of healthy subjects and can differentiate between early , moderate , and advanced glaucoma .
the gcc and gcipl parameters from both ss - oct and sd - oct carry a diagnostic performance at least equal to that of circumpapillary rnfl parameters ; all three parameters , including mrnfl , now have comparable diagnostic performance in detection of preperimetric glaucoma . once vf losses are apparent , there is a significant association of vf defect patterns with gcipl defect patterns .
the most commonly observed gcipl and inner macular layer defect pattern in glaucoma subjects is thinning in the inferior perifoveal region , seen clinically as superior vf defects ( figs . 2 , 3 ) .
ganglion cell analysis from cirrus - oct ( carl - zeiss meditec , dublin , ca , usa ) , which includes the combination of ganglion cell and inner plexiform layers ( gcipl ) , shows thinning in the inferior and inferotemporal perifoveal regions of both eyes .
macular parameters are of increasing importance in the management of glaucoma , especially given improvements in oct technology .
recent software updates have reduced gcc segmentation errors in patients with macular degeneration , which should allow these patients to be evaluated for glaucoma with more confidence .
posterior pole asymmetry analysis ( ppaa ) combines mapping of the posterior pole retinal thickness with asymmetry analysis between eyes and between hemispheres of each eye .
posterior pole asymmetry analysis , although not presently having a built - in normative database , is highly reproducible and matches circumpapillary rnfl measurements in terms of diagnostic accuracy of early glaucoma .
spectral - domain oct may also be superior to ss - oct in detecting gcipl thinning in the outer temporal zone , where the glaucomatous damage commonly occurs .
however , sd - oct and ss - oct have similar glaucoma diagnosis abilities based on macular inner layer thickness analysis .
ultimately , clinical assessment of the macular region is helpful in glaucoma diagnosis and evaluation and clinicians should incorporate macular scans into clinical protocols
. patients with abnormal or borderline macular structural parameters likely require close follow - up and initiation of treatment to avoid vision loss .
in addition to glaucoma , other macular diseases are also common in the aging population .
these conditions may affect oct macular thickness measurements and render them useless for the evaluation of glaucoma , including diabetic retinopathy , macular edema , macular degeneration , and epiretinal membranes .
advances in oct technology have also allowed for higher - resolution imaging of the onh and quantification of onh parameters , but the clinical value of oct onh parameters remains controversial . compared with previous oct technology , sd - oct relies less on data interpolation , and this has resulted in far better delineation of onh structures than could be achieved with td - oct .
studies have found that onh parameters have an excellent ability to discriminate between normal eyes and eyes with even mild glaucoma .
parameters such as rim area , vertical rim thickness , and vertical cup to disc ratio were found to have the greatest diagnostic ability and were as good as rnfl thickness parameters in diagnosing glaucoma . in some cases ,
onh parameters were found to be better at initial glaucoma detection and discriminating glaucoma and glaucoma suspect subjects from normal subjects .
however , a number of studies show onh parameters are inferior to standard circumpapillary measurements for glaucoma detection .
one study , although limited by using vfs as a reference standard , found that rnfl and macular parameters were significantly better for glaucoma diagnosis than onh parameters , especially for early - stage glaucoma .
differences in these results are at least partially a consequence of the reference standard used to select cases and controls given that a reference standard must be employed to select cases and controls for any diagnostic accuracy study .
there is a greater chance , for example , that patients with clearly abnormal optic disc features will be classified as cases if the reference criteria include optic disc appearance .
this type of reference standard introduces a bias towards favoring accuracy of topographic onh parameters .
furthermore , differences in commercially available oct devices could at least partially explain the differences between studies , such as differences in the acquisition speed , scanning rate , spatial resolution , layer detection algorithms , and analytical software .
each of the different devices , therefore , may report different rnfl thickness values and onh measurements .
additional reasons could also contribute to variable results , including differences in the number of subjects , differences in ethnicity , or differences in the representation of the different stages of glaucoma .
consideration of a combination of circumpapillary and onh parameters is likely the best approach for glaucoma detection . given recent advances in sd - oct technology , evaluating the onh with oct is useful in the diagnosis and management of glaucoma .
segmentation of the onh was greatly improved with new software , as was implementation of referencing the fovea 's position and bruch 's membrane as anatomic landmarks , which allowed for better measurement of the onh rim and rnfl thickness .
bruch 's membrane opening minimal rim width ( bmo - mrw ) , a relatively new anatomical parameter describing the neuroretinal rim , consists of the minimum distance between the bmo and the internal limiting membrane .
bruch 's membrane opening minimal rim width has a high association with glaucomatous functional changes on sap and , compared with previous bmo methods , has a better ability to detect early glaucoma .
it has an advantage over other sd - oct methods of neuroretinal thickness measurement by considering the variable orientation of rim tissue in the onh .
rim area , however , appears to be a more useful onh parameter for detecting early glaucoma .
ultimately , assessment of circumpapillary rnfl , macular , and onh parameters is useful for quantifying risk , diagnosis , and management of glaucoma at different levels of severity .
detection of disease progression remains challenging in glaucoma due to the variable and slowly progressive nature of the disease , measurement variability of sap and of imaging devices , and the lack of a commonly acceptable reference standard .
some eyes show structural changes in the onh or rnfl before any indication of glaucomatous damage can be detected with sap . because sd - oct is relatively new technology ,
only a few reports exist using sd - oct rnfl parameters for detecting glaucoma progression .
most progression studies use td - oct due to the longer follow - up period .
assessment of multiple oct parameters from the macula , onh , and rnfl is important , not only in diagnosis , but to detect disease progression and longitudinal change .
retinal nerve fiber layer evaluation is less sensitive than vf when tracking progression in advanced cases due to a floor effect that occurs when the residual rgc layer has nearly diminished .
although average rnfl thickness may be the main parameter to consider when evaluating for structural progression in advanced glaucoma patients , rnfl thicknesses in the inferior quadrant and inferotemporal sector may be the most predictive of progression ( fig .
retinal nerve fiber layer thinning in the superior quadrant has also been associated with subsequent vf losses in td - oct .
spectral - domain oct instruments can not be used interchangeably , however , especially for glaucoma progression assessment , due to variability in circumpapillary rnfl thickness calculations .
interestingly , other studies found that average macular thickness is more sensitive than circumpapillary rnfl for detection of disease progression
. additionally , analysis of the total retinal thickness ( gcipl , along with outer plexiform layer to rpe ) may be more sensitive in detecting progression than circumpapillary rnfl .
guided progression analysis from cirrus - oct ( carl - zeiss meditec ) demonstrating early glaucomatous progression .
compared with baseline examinations from december 2007 , the patient has statistically significant focal rnfl loss in the inferior quadrant in the left eye .
more commonly , the corresponding rnfl thickness map to  exam 6  may show a red wedge - shaped defect in the inferior quadrant of the onh .
approaches that combine structure and function improve diagnosis both in cross - sectional and longitudinal investigations and algorithms that combine structural and functional measurements will likely improve the detection of glaucoma progression .
prior studies suggest that using a combination of perimetry and circumpapillary rnfl values is the best approach when monitoring for progression , especially given that sd - oct rnfl values have a strong relationship to functional deficits . in td - oct ,
structural progression was associated with functional progression in preperimetric , glaucoma suspect , and glaucomatous eyes and eyes with significant sap progression have higher rates of rnfl thickness loss compared with nonprogressing eyes .
clinically , it can be difficult to determine whether rnfl losses that precede sap changes reflect true progression .
important from a clinical perspective , the 24 - 2 vf test , although the gold standard in sap for glaucoma evaluation , is not an ideal strategy for detecting glaucomatous damage of the macula ; the 10 - 2 vf will often detect damage missed with the 24 - 2 pattern .
as oct evolves , it will continue to provide more accurate detection of progression and enhance our understanding of the structural pathogenesis of glaucoma , including the role of the lc in glaucoma progression . as the presumed site of axonal injury in glaucoma , the lc may play a role in neuronal death seen in glaucoma .
lamina cribrosa microstructure likely provides the mechanical support to optic nerve fibers within the deep optic disc region .
quantitative measurements of lc microarchitecture , such as pore diameter , pore area , and lc beam thickness , were found to have good reproducibility in a multimodal sd - oct with adaptive optics technology and offer the potential to serve as biomarkers for glaucoma progression . using a prototype ss - oct with 100,000 a - scan /
s scanning speed and 5-m axial resolution , wang et al . demonstrated good reproducibility of lc parameters , including pore diameter sd , pore aspect ratio ; beam thickness , pore area , beam thickness sd , and beam thickness to pore diameter ratio .
lamina cribrosa microarchitecture changes have been observed with ss - oct in glaucomatous eyes , and lc pore shape and size also have been correlated with the severity and progression of glaucoma .
additionally , the lc was found to be displaced both anteriorly and posteriorly in glaucomatous eyes compared with age - matched healthy eyes , and thinner lc was associated with glaucoma progression .
overall , the structural thinning and displacement of the lc likely cause lc pores to deform , impeding axoplasmic flow within the optic nerve fibers and disrupting transport of factors crucial for the survival of rgcs .
in addition , there may be biological changes that occur due to deformations of the lamina in the axons or microglia that result in axonal stress or rgc impairment or death .
although the lc 's role in glaucoma progression is yet to be fully determined , ss - oct and sd - oct have undoubtedly improved current understanding of the lc and its microarchitecture .
optical coherence tomography has impacted the ways that patients are diagnosed and followed clinically and remains a dynamic and evolving imaging modality . optical coherence tomography technology and software algorithms are improving and newer technologies are continually under development , increasing oct 's clinical utility .
clinicians should be aware of oct 's limitations and should be aware of possible scan artifacts .
clinical decisions should never be driven by oct results alone , but should also be based on a complete ophthalmic examination and vf assessment .
 optical coherence tomography ( oct ) has established itself as the dominant imaging modality in the management of glaucoma and retinal diseases , providing high - resolution visualization of ocular microstructures and objective quantification of tissue thickness and change . 
 this article reviews the history of oct imaging with a specific focus on glaucoma . 
 we examine the clinical utility of oct with respect to diagnosis and progression monitoring , with additional emphasis on advances in oct technology that continue to facilitate glaucoma research and inform clinical management strategies . 
Diagnosis of Glaucoma
Detecting Progression
Conclusions