Glaucoma: a disease of the macula?

Transcription

1 Glaucoma: a disease of the macula? Derek MacDonald, OD, FAAO Waterloo, Ontario, Canada Please silence all mobile devices and remove items from chairs so others can sit. Unauthorized recording of this session is prohibited.

2 Disclosure Statement: Honoraria: Alcon Allergan Carl Zeiss Meditec The content and format of this course is presented without commercial bias and does not claim superiority of any commercial product or service

3 The traditional paradigm Glaucoma is an optic neuropathy that causes mid-peripheral visual field loss, sparing the central field until end stage disease Conventional diagnostic testing included clinical assessment of the optic nerve and RNFL, and 24- or 30-2 visual field analysis

4 An evolving paradigm The evolution of optical coherence tomography enabled more objective analysis of the ONH and RNFL

5 A (not so) new paradigm Since the late 1960s it has been recognized that glaucoma can cause initial VF defects that threaten fixation 1 However, macular involvement received little attention because conventional analyses were poorly suited to detect it Now, OCT assessment of macular retinal ganglion cell thickness has rekindled interest in glaucomatous damage of the macula 1. Drance SM. The early field defects in glaucoma. Invest Ophthalmol 1969;8:84-91.

6 Why is macular involvement important? Despite representing only 2% of the total retinal surface, the macula contains over 30% of the RGCs in the human retina, and is mapped to an area occupying 60% of the visual cortex Curcio CA, Allen KA. Topography of ganglion cells in human retina. J Comp Neurol 1990;300: De Moraes CG, et al. Defining 10-2 visual field progression. Ophthalmology 2014;121: Adams DL, Horton JC. A precise retinotopic map of primate striate cortex generated from the representation of angioscotomas. J Neurosci 2003;23:

7 Why is macular involvement important? Visual field loss within 10 of fixation: is part of the definition of advanced (severe) glaucoma 1 has a significant impact on activities of daily living 2 necessitates aggressive intervention to minimize progression Glaucomatous damage of the macula is common in early disease, but can easily go undetected by current (conventional) analyses 3 1. Canadian Ophthalmological Society Glaucoma Clinical Practice Guideline Expert Committee. COS evidence-based clinical practice guidelines for the management of glaucoma in the adult eye. Can J Ophthalmol 2009;44:S Blumberg DM, et al. Association between undetected 10-2 visual field damage and vision-related quality of life in patients with glaucoma. JAMA Ophthalmol 2017; doi /jamaophthalmol Hood DC, et al. The nature of macular damage in glaucoma as revealed by averaging optical coherence tomography data. Trans Vis Sci Tech 2012;1:doi: tvst

8 Macular damage is common More than 50% of the eyes with mild to moderate glaucomatous field loss showed defective locations in the superior paracentral region within an eccentricity of 3. 1 Macular damage, as seen on 10-2 VFs, appears to occur almost as frequently as peripheral defects in patients with early glaucoma. 2 Given the prevalence of early macular damage, patients should not be screened with only the 24-2 VF Schiefer U, et al. Spatial pattern of glaucomatous visual field loss obtained with regionally condensed stimulus arrangements. Invest Ophthalmol Vis Sci 2010;51: Traynis I, et al. Prevalence and nature of early glaucomatous defects in the central 10 of the visual field. JAMA Ophthalmol 2014;132: Grillo LM, et al. The 24-2 visual field test misses central macular damage confirmed by the 10-2 visual field test and optical coherence tomography. Trans Vis Sci Tech 2016;5:doi: /tvst

9 Macular damage is overlooked A 24-2 grid has 54 points (only 4 in the central 8 ) separated by 6 A 10-2 grid has 68 points (all in the central 10 ) separated by 2 A paracentral scotoma can fall between the cracks of the ,2 1. Asaoka R. Measuring visual field progression in the central 10 degrees using additional information from central 24 degrees visual fields and lasso regression. PLoS One 2013;12:e72199.doi:1371/ journal.pone Traynis I, et al. Prevalence and nature of early glaucomatous defects in the central 10 of the visual field. JAMA Ophthalmol 2014;132:291-7.

10 RGC displacement at the fovea RPE Fovea In this histological section, a 0.52mm from the fovea is separated from its by nearly 0.6mm due to the length of the intermediate Henle fiber ( arrowheads) and RGC dendrite ( arrowheads) 1 1. Drasdo N, et al. The length of Henle fibers in the human retina and a model of ganglion receptive field density in the visual field. Vis Res 2007;47:

11 RGC displacement and a 6 grid The central 10 is poorly sampled by the 24-2 grid, particularly after RGC displacement at the fovea is accounted for (on right) 1 Note the that would be missed by the 24-2 grid 1. Hood DC, et al. The nature of macular damage in glaucoma as revealed by averaging optical coherence tomography data. Trans Vis Sci Tech 2012;1:doi: tvst

12 RGC displacement and a 2 grid The 10-2 grid is better, but still samples the area immediately adjacent to fixation relatively poorly after RGC displacement is accounted for (on right) 1 1. Hood DC, et al. The nature of macular damage in glaucoma as revealed by averaging optical coherence tomography data. Trans Vis Sci Tech 2012;1:doi: tvst

13 24-2 versus 10-2 defects A single abnormal paracentral point on 24-2 analysis may prove to be a characteristic superior arcuate scotoma on Park HY, et al. Clinical clues to predict the presence of parafoveal scotoma on Humphrey 10-2 visual field using a Humphrey 24-2 visual field. Am J Ophthalmol 2016;161:150-9.

14 24-2 versus 10-2 defects A paracentral scotoma can fall between the cracks of the % of eyes with a normal 24-2 showed an abnormal 10-2 Scotoma caught on both 24-2 and 10-2 Scotoma caught on 10-2 but missed on 24-2 Scotoma caught on 24-2 but missed on Traynis I, et al. Prevalence and nature of early glaucomatous defects in the central 10 of the visual field. JAMA Ophthalmol 2014;132:291-7.

15 Complementary analyses Nearly 62% of eyes with early glaucoma classified as testing showed testing 1 a large proportion of eyes within the glaucoma continuum have abnormal 10-2 visual field results despite normal 24-2 results many patients called suspects or preperimetric may in fact have established glaucomatous functional damage On the other hand, 85% of eyes with early glaucoma classified as testing showed testing Therefore, it s not a question of 24-2 or 10-2 it s 1. De Moraes CG, et al visual fields miss central defects shown on 10-2 tests in glaucoma suspects, ocular hypertensives, and early glaucoma. Ophthalmology 2017;doi: /j.ophtha

16 Structure/function correlation Glaucomatous VF loss results from damage to the RGC axons at the level of the lamina cribrosa of the ONH The characteristic shape and location of these is determined by the anatomy of the RNFL 1,2 arcuate scotoma temporal wedge nasal step paracentral defect 1. Hart WM, Becker B. The onset and evolution of glaucomatous visual field defects. Ophthalmology 1982;89: Keltner JL, et al. Classification of visual field abnormalities in the Ocular Hypertension Treatment Study. Arch Ophthalmol 2003;121:

17 Structure/function correlation Superimposing the 24-2 grid on photographs of well-defined RNFL defects allowed VF locations to be mapped to regions of the ONH, correlating functional loss with structural change 1 1. Garway-Heath DF, et al. Mapping the visual field to the optic disc in normal tension glaucoma eyes. Ophthalmology 2000;107:

18 24-2 Structure/function correlation

19 Macular vulnerability zone Most axons from the inferior-temporal macula project to the, while those from the superior macula project to the less vulnerable temporal quadrant 1,2 Less vulnerable macular region projects to the temporal quadrant More vulnerable macular region projects to the inferior quadrant 1. Hood DC, et al. Glaucomatous damage of the macula. Prog Retin Eye Res 2013;32C: Hood DC, et al. Early glaucoma involves both deep local, and shallow widespread, retinal nerve fiber damage of the macular region. Invest Ophthalmol Vis Sci 2014;55:

20 Inferior macular damage N S T I N RGC damage in the inferior macula can be extreme and central, leading to superior VF loss that is deep and threatens fixation 1 RNFL analysis (as an NSTIN curve, putting the macula centrally) shows at the border of the temporal and inferior quadrants: the 1. Hood DC, et al. Early glaucoma involves both deep local, and shallow widespread, retinal nerve fiber damage of the macular region. Invest Ophthalmol Vis Sci 2014;55:

21 Seeing macular involvement: TSNIT versus NSTIN T S N I T N S T I N

22 Superior macular damage N S T I N In contrast, RGC damage in the superior macula tends to be more subtle, leading to shallower inferior VF loss further from fixation 1 As such, RNFL analysis can appear nearly normal, showing a at the border of the temporal and superior quadrants 1. Hood DC, et al. Early glaucoma involves both deep local, and shallow widespread, retinal nerve fiber damage of the macular region. Invest Ophthalmol Vis Sci 2014;55:

23 Diffuse macular damage N S T I N Macular damage can also be diffuse, with and shallow VF depression 1 diffuse macular damage is easily overlooked Even with diffuse damage, the inferior macula is more involved: note the and more extreme RNFL thinning in the inferior 1. Hood DC, et al. Early glaucoma involves both deep local, and shallow widespread, retinal nerve fiber damage of the macular region. Invest Ophthalmol Vis Sci 2014;55:

24 Patterns of macular damage Damage to axons in the results in a superior arcuate defect that threaten fixation 1 Examples of early, moderate, and advanced defects on 10-2 AVF 1. Sullivan-Mee M, et al. Prevalence, features, and severity of glaucomatous visual field loss measured with the 10-2 achromatic threshold visual field test. Am J Ophthalmol 2016;168:40-51.

25 The MVZ explains patterns of macular damage The region within the the corresponds to the of the 10-2 grid corresponds to, while the region within the 1. Hood DC, et al. Glaucomatous damage of the macula. Prog Retin Eye Res 2013;32C:1-21.

26 Paracentral scotoma progression Paracentral arcuate scotomas deepen 3 to 5 above fixation, then spread laterally 1 Only two 24-2 points sample the area representing the inferior macular vulnerability zone 2 As a result, over 70% of eyes with paracentral scotomas progressing on 10-2 were missed by 24-2 (see above) 3 1. Su D, et al. Progression patterns of initial parafoveal scotomas in glaucoma. Ophthalmology 2013;120: Hood DC, De Moraes CG. Challenge to the common clinical paradigm for diagnosis of glaucomatous damage damage with OCT and visual fields. Invest Ophthalmol Vis Sci 2018;59: Park SC, et al. Parafoveal scotoma progression in glaucoma. Humphrey 10-2 versus 24-2 visual field analysis. Ophthalmology 2013;120:

27 RNFL scans underestimate macular damage Focusing only on summary (global) measures of RNFL thickness or temporal quadrant thickness often misses macular damage 1 Scrutinizing clock hour 7 of the RNFL thickness profile improves detection by capturing most of the MVZ, but still misses nearly 40% of subtle macular damage clearly seen with macular RGC and 10-2 analyses 2 in addition to the disc cube scan, macula scans should be incorporated into clinical protocols for detecting glaucomatous damage 1. Wang DL, et al. Central glaucomatous damage of the macula can be overlooked by conventional OCT retinal nerve fiber layer thickness analyses. Trans Vis Sci Tech 2015;4:doi: /tvst Kim YK, et al. Inferior macular damage in glaucoma: its relationship to retinal nerve fiber layer defect in macular vulnerability zone. J Glaucoma 2017;26:

28 Evaluating macular OCT The macula shows less anatomic variability than the ONH/RNFL particularly valuable in the presence of an anomalous ONH and/or high myopia 1,2 less helpful in the presence of concurrent macular disease 3 An on-axis macular scan is also easier for patient and technician Evaluate minimum and inferior-temporal GCIPL thickness Sung KR, et al. Progression detection capability of macular thickness in advanced glaucomatous eyes. Ophthalmology 2012;119: Shoji T, et al. Assessment of glaucomatous changes in subjects with high myopia using spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci 2011;52: Hwang YH, et al. Segmentation errors in macular ganglion cell analysis as determined by optical coherence tomography. Ophthalmology 2016;123: Mwanza JC, et al. Glaucoma diagnostic accuracy of ganglion cell-inner plexiform layer thickness: comparison with nerve fiber layer and optic nerve head. Ophthalmology 2012;119: Sullivan-Mee M, et al. Diagnostic precision of retinal nerve fiber layer and macular thickness asymmetry parameters for identifying early primary open-angle glaucoma. Am J Ophthalmol 2013;156:

29 Evaluating macular OCT Cirrus Ganglion Cell Analysis showing inferior GCIPL thinning in the left eye (temporal>nasal): asymmetry across the horizontal raphe causing a superior paracentral scotoma near fixation 1 1. Kim YK, et al. Glaucoma-diagnostic ability of ganglion cell-inner plexiform layer thickness difference across temporal raphe in highly myopic eyes. Invest Ophthalmol Vis Sci 2016;57:

30 Structure/function: RNFL/24-2

31 Structure/function: GCIPL/10-2

32 Objective imaging caveats DeLeon-Ortega JE, et al. Discrimination between glaucomatous and nonglaucomatous eyes using quantitative imaging devices and subjective optic nerve head assessment. Invest Ophthalmol Vis Sci 2006;47: Chong GT, Lee RK. Glaucoma versus red disease: imaging and glaucoma diagnosis. Curr Opin Ophthalmol 2012;23:79-88.

33 Paracentral OAG? An OAG subtype that attacks central vision characterized by: lower untreated IOP (although not only NTG) 1 prelaminar NFL defects within the cup noted on OCT 2 frequent disc hemorrhages systemic hypotension Raynaud s phenomenon; migraine; sleep apnea (?) genetic predisposition to impaired nitric oxide regulation 3,4 Patients with paracentral OAG require aggressive IOP reduction 1. Park SC, et al. Initial parafoveal versus peripheral scotomas in glaucoma: risk factors and visual field characteristics. Ophthalmology 2011;118: Taniguchi E, et al. Prelaminar and lamina cribrosa defects detected by swept source OCT in glaucoma stratified by visual field loss pattern. Invest Ophthalmol Vis Sci 2015;56: Loomis SJ, et al. Association of CAV1/CAV2 genetic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss. Ophthalmology 2014;121: Kang JH, et al. Association of dietary nitrate intake with primary open-angle glaucoma. JAMA Ophthalmol 2016;134:

34 Patient OD History 68 y/o Caucasian woman general health: good (ACEI for hypertension) family history: diabetes ophthalmic history: unremarkable low ATR astigmatism with good BCVA (6/6) normal binocularity, pupil reactions, and confrontation VFs normal anterior segment structures November 2009 IOPs 17/19 CCTs 524/528

35 Patient OD December 2009 untreated IOPs: 15/19

36 Patient OD June 2011 untreated IOPs: 18/21

37 Patient OD December 2009 IOP: 19 April 2013 IOP: 22

38 Patient OD April 2013 untreated IOPs: 20/22

39 Patient OD April 2013 IOP: 22 October 2013 IOP: 24

40 Patient OD March 2014 IOP: 21 May 2014 IOP: 21

41 Patient OD September 2015 IOP: 22 Sept IOP: 22

42 Patient OD January 2017 IOP: 20 Feb IOP: 20

43 Patient OD 24-2 GPA (2009 to 2017): event-based progression near fixation

44 Patient OD 24-2 summary ( ): paracentral scotoma progression

45 Patient OD GCIPL GPA & 10-2 summary ( ): structure & function Δ

46 The future of OCT Swept-source OCT (SS-OCT) and image integration will allow simultaneous imaging/analysis of RNFL and macular RGC 1 Single-page (Hood) report from a single wide-field Topcon SS-OCT scan Zeiss Panomap integration of individually acquired RNFL and GCIPL scans (for patient OD) 1. Hood DC, et al. A single wide-field OCT protocol can provide compelling information for the diagnosis of early glaucoma. Trans Vis Sci Tech 2016;5:doi: tvst

47 The future of OCT Swept-source OCT (SS-OCT) and image integration will allow simultaneous imaging or analysis of RNFL and macular RGC 1 Single-page (Hood) report from a single wide-field Topcon SS-OCT scan Zeiss Forum combined report showing structure/function correlation (for patient OD) 1. Hood DC, et al. A single wide-field OCT protocol can provide compelling information for the diagnosis of early glaucoma. Trans Vis Sci Tech 2016;5:doi: tvst

48 The future of AVF Adding strategic points to the 24-2 AVF grid (perhaps from the 10-2 grid; mirroring RNFL distribution; weighting central points) may assist in diagnosing and monitoring macular damage 1 Modifying the conventional 24-2 grid with a subset of 10-2 points (examples above) or using the Octopus G-pattern (to right) can improve detection of macular damage 2 1. Hood DC, et al. A test of a model of glaucomatous damage of the macula with high-density perimetry: implications for the locations of visual field test points. Trans Vis Sci Tech 2014;3:doi: /tvst Ehrlich AC, et al. Modifying the conventional visual field test pattern to improve the detection of early glaucomatous defects in the central 10. Trans Vis Sci Tech 2014;3:doi: /tvst.3.6.6

49 But what should we do now? Macular and RNFL analyses are complementary, and GCIPL thinning can precede RNFL loss 1,2 Current OCT segmentation algorithms aren t foolproof: carefully inspect each scan to ensure its accuracy 3,4 ensure quality: strong signal, no movement/blink artifacts 5 recognize the limitations of reference databases 6 Never rely solely on summary parameters: and in both RNFL and macular scans 7 1. Kim YK, et al. Inferior macular damage in glaucoma: its relationship to retinal nerve fiber layer defect in macular vulnerability zone. J Glaucoma 2017;26: Kim YK, et al. Temporal relationship between macular ganglion cell-inner plexiform layer loss and peripapillary retinal nerve fiber layer loss in glaucoma. Ophthalmology 2017;124: Hood DC, Raza AS. On improving the use of OCT imaging for detecting glaucomatous damage. Br J Ophthalmol 2014;98:ii1-ii9. 4. Rao HL, et al. Effect of scan quality on diagnostic accuracy of spectral-domain optical coherence tomography in glaucoma. Am J Ophthalmol 2014;157: Chong GT, Lee RK. Glaucoma versus red disease: imaging and glaucoma diagnosis. Curr Opin Ophthalmol 2012;23: Realini T, et al. Normative databases for imaging instrumentation. J Glaucoma 2015;24: Hood DC, De Moraes CG. Four questions for every clinician diagnosing and monitoring glaucoma. J Glaucoma 2018;27:

50 But what should we do now? 24- and 10-2 VF analyses are also complementary Macular damage, as seen on 10-2 VFs, appears to occur almost as frequently as peripheral defects in patients with early glaucoma. 1 Particularly with: loss of inferior GCIPL 3 central abnormality in the 24-2 grid 4 symptoms not commensurate with 24-2 status 5 glaucomatous optic neuropathy at lower IOP 6 disc hemorrhages systemic hypotension/migraine/raynauds/osa 2 1. Traynis I, et al. Prevalence and nature of early glaucomatous defects in the central 10 of the visual field. JAMA Ophthalmol 2014;132: Grillo LM, et al. The 24-2 visual field test misses central macular damage confirmed by the 10-2 visual field test and optical coherence tomography. Trans Vis Sci Tech 2016;5(2): Hood DC, et al. The nature of macular damage in glaucoma as revealed by averaging optical coherence tomography data. Trans Vis Sci Tech 2012;1:3. 4. Park HY, et al. Clinical clues to predict the presence of parafoveal scotoma on Humphrey 10-2 visual field using a Humphrey 24-2 visual field. Am J Ophthalmol 2016;161: Blumberg DM, et al. Association between undetected 10-2 visual field damage and vision-related quality of life in patients with glaucoma. JAMA Ophthalmol 2017; doi /jamaophthalmol Hood DC, De Moraes CG. Four questions for every clinician diagnosing and monitoring glaucoma. J Glaucoma 2018;27:

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