Macular Ganglion Cell Loss In Ocular Disorders

The Structure/Function Conundrum

Written by Larry J Alexander OD FAAO Wednesday, 12 December 2012

- Glaucoma is a neurodegenerative disease causing the loss of retinal ganglion cells
- Ganglion cell numbers range from approximately .7 million to 1.5 million
- Density is greatest in the macula where the ganglion cell layer can be 6 cells deep
- The thinnest and densest layer of ganglion cells is in a 1 to 1.5 mm radius of the fovea

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GANGLION CELL LOSS IN THE MACULA

  • Histologic studies have shown ganglion cell loss in the macula in glaucoma
  • Desatnik et al. (1996) found macular ganglion cells are lost in early glaucoma
  • Yucel et al. (2003) showed loss of cells in the parvocellular layers of the LGN implicating central ganglion cell loss…the damage actually goes backward into the neuro system

Desatnik H, Quigley HA, Glovisnky Y. J Glaucoma 1996; 5: 46-53. Yucel YH, Zhang Q, Weinreb RN, Kaufman PL, Gupta N. Prog Retin Eye Res 2003; 22:465-481

MACULA THINNING IN GLAUCOMA

  • Greenfield et al (2003) showed thinning of the macula in glaucoma patients using Time Domain (TD) OCT (Stratus)
  • Guedes et al. (2003) also found significant macula thinning in glaucoma patients compared to normals with TD OCT

CASE

  • 25 yo
  • c/o blurred vision that seems to be getting worse
  • “should i continue in college or am i going blind?” dad doesn’t see too well and was told he has macular degeneration.
  • BCVA O.U. 20/30 with o.D. -4.75-1.25 x 155 and o.S. -3.50-2.25x 005
  • IOP20 mm hg o.U.
  • 20/20 vision in the past, confirmed by call to previous doctor

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DIAGNOSTIC ACCURACY WITH TD OCT: MACULA VS RNFL

  • Medeiros et al. (2005) found the diagnostic accuracy of peripapillary RNFL thickness was significantly more accurate than macula thickness (AROC = 0.91 for RNFL, 0.81 for macula)
  • Wollstein et al. (2005) found similar results where RNFL thickness was significantly more accurate for detecting glaucoma than macula thickness

Medeiros FA, Zangwill M, Bowd C et al. Am J Ophthalmol. 2005; 139:44-55 Wollstein G, Ishikawa H, et al. Am J Ophthalmol 2005; 139: 39-43.

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TD OCT STUDY LIMITATIONS

  • Major disadvantage in these studies is that TD OCT typically measures full retinal thickness only (does not isolate ganglion cells)
  • TD OCT does not have enough depth resolution to image and segment the ganglion cells accurately and reliably

SDOCT ADVANTAGE

  • SDOCT has twice the depth resolution as TD OCT (5 microns vs 10 microns)
  • Allows imaging and segmentation of ganglion cell layers…which then better highlights depressions
  • Faster speed also allows for greater density of sampling points and reduces artifacts from eye-movements (SDOCT has 26,000 A scans/sec vs Stratus TD OCT with 400 A scans/sec)

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 CAN IMAGING THE GANGLION CELLS IN MACULA WITH SDOCT IMPROVE GLAUCOMA DETECTION?

DIAGNOSTIC ACCURACY: GCC VS TD OCT FULL RETINA THICKNESS IN MACULA

  • Tan et al. (2009) found the GCC (RTVue FD OCT) was significantly more accurate for detecting glaucoma compared to fovea thickness (full macula thickness) with Stratus TD OCT (AROC = 0.90 for GCC vs 0.85 for TD OCT)
  • Mori et al. (2010) also showed GCC was significantly more accurate than full macula thickness with TD OCT (AROC = 0.922 for GCC vs 0.84 for full retina thickness)

Tan O, Chopra V, Lu AT et al. Ophthalmology 2009; 116:2305-2314. Mori S, Hangai M, et al. 2010; J Glaucoma, in press.

DIAGNOSTIC ACCURACY: GCC VS SDOCT RNFL

  • Rao et al. (2010) found GCC had similar accuracy levels as RTVue FD RNFL (AROC = 0.81 for GCC vs 0.88 for RNFL)
  • Seong et al. (2010) found similar results (AROC = 0.95 for GCC and 0.97 for RNFL)
  • Kim et al. (2010) found AROC values were higher for RNFL vs GCC in a group of advanced glaucoma patients (AROC = 0.92 for GC vs 0.96 for RNFL), but GCC values were higher than RNFL in a group of early glaucoma patients (AROC = 0.83 for GCC vs 0.78 for RNFL)

Rao HL, Zangwill LM, Weinreb RN et al. Ophthalmology 2010; in press. Seong M, Sung KR, Choi EH, et al. Invest Ophthalmol Vis Sci 2010; 51:1446-1452. Kim NR, Lee ES, Sung GJ, et al. Invest Ophthalmol Vis Sci 2010; in press

RTVUE SDOCT: GCC VS DISC VS RNFL

  • Huang et al. (2010) compared the diagnostic accuracy for GCC, optic disc, and RNFL from the RTVue
  • AROC for RNFL was highest (AROC = 0.92), with GCC second (AROC = 0.86), and vertical C/D ratio a close third (AROC = 0.854)
  • They found the accuracy improved when they combined all three structures in an LDF (AROC = 0.97)

Huang JY, Pekmezci M, Mesiwala N, Kao A, Lin S. J of Glaucoma 2010 Epub ahead of print

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SUMMARY OF DIAGNOSTIC ACCURACY RATES

In recent evaluations of the glaucoma diagnostic accuracy of OCT, sensitivity values of 78% to 92% for Cirrus OCT and 80% to 88% for RTVue with specificities of 77% to 95% for Cirrus and 90% to 98% for RTVue, respectively, have been reported

Bengtsson B, Andersson S, Heijl A. Performance of time-domain and spectral-domain optical coherence tomography for glaucoma screening. Acta Ophthalmol. 2012;90:310-315.

Chang RT, Knight OJ, Feuer WJ, et al. Sensitivity and specificity of time-domain versus spectral-domain optical coherence tomography in diagnosing early to moderate glaucoma. Ophthalmology. 2009;116:2294-2299.

Mwanza JC, Oakley JD, Budenz DL, et al. Ability of Cirrus HD-OCT optic nerve head parameters to discriminate normal from glaucomatous eyes. Ophthalmology. 2011;118:241-248.

Rao HL, Zangwill LM, Weinreb RN, et al. Comparison of different spectral domain optical coherence tomography scanning areas for glaucoma diagnosis. Ophthalmology. 2010;117:1692-1699.

Sehi M, Grewal DS, Sheets CW, et al. Diagnostic ability of Fourier-domain vs time-domain optical coherence tomography for glaucoma detection. Am J Ophthalmol. 2009;148:597-605. 

DIAGNOSTIC ACCURACY RATES IN MYOPIA

With both Cirrus and RTVue it is reported that the rate of abnormal RNFL and Ganglion Cell Layer Scans was fairly high. This was judged not to make the tests useless, but rather issues a caution to consider all factors when scanning myopic eyes. It is suggested that this is secondary to thinned RNFL and GCC in these patients compounded by other anatomical characteristics.

Mwanza JC, Sayyad FE, Aref AA, Budenz KL. Rates of abnormal retinal nerve fiber layer and ganglion cell layer OCT scans in healthy myopic eyes: Cirrus versus RTVue. Ophthalmic Surg Lasers Imaging 2012;43:S67-S74.

 CORRELATION WITH VISUAL FIELDS

  • Mori et al. (2010) showed GCC correlated more strongly with visual field MD values compared to full retinal thickness with SDOCT (r = 0.58 for GCC vs 0.46 for macula)

Mori S, Hangai M, et al. 2010; J Glaucoma, in press.


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GCC SUMMARY

  • GCCthickness correlates well with visual fields
  • Highly reproducible
  • More reproducible and more accurate for detecting glaucoma than macula thickness with td oct
  • Similar accuracy for detecting glaucoma as sdoct rnfl thickness

 

WHAT CHANGES FIRST?

  • Structure damage often precedes functional damage in glaucoma1
  • RNFL loss often precedes optic disc changes2
  • Can GCC change before RNFL?
  1. Sommer A. et al. Clinically detected nerve fiber atrophy precedes the onset of glaucomatous field loss. Arch Ophthalmol 1991; 109:77-83.
  2. Quigley HA, Katz J et al. Ophthalmology 1992; 99: 19-28.

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CASES TO ILLUSTRATE GCC AND THE STRUCTURE/FUNCTION CONUNDRUM

CASE

  • 30 YEAR OLD
  • ROUTINE EYE EXAM
  • IOP 18 MM HG O.U.
  • GLAUCOMA SUSPECT?

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ANALYSIS

  • Is the rnfl analysis an aberration of the testing of extremely large discs?
  • Is the cd ratio an aberration of the testing of extremely large discs
  • This is structure only testing and of only one parameter
  • What is missing?

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ANALYSIS

  • VERY LARGE DISCS…OS (3.91) >OD (3.41)
  • VERY LARGE CUPS
  • QUESTIONABLE RNFL AND TSNIT
  • WHAT IS THE STATUS OF THE ANGLE?
  • WHAT IS THE STATUS OF THE CORNEAL THICKNESS?
  • WHAT IS THE STATUS OF THE VISUAL FIELD?
  • IMAGING IS NOT A ONE-TRICK PONY FOR DIFFERENTIAL DIAGNOSIS


CASE

  • 56 YEAR OLD
  • HX LOW TENSION GLAUCOMA
  • BASELINE IOP OF 19/20 MM HG
  • PACHS OF 524 AND 520 MICRONS
  • ON LUMIGAN Q HS WITH IOP OF 14 MM HG
  • BEST VA OF 20/20 O.U.

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CASE SUMMARY

  • GCC & RNFL LOSS OU CORRESPONDS VERY WELL WITH VF LOSS & ASSESSMENT OF OPTIC DISC PHOTOGRAPHS
  • ANGLE ASSESSMENT?


CASE

  • 61 YO
  • ROUTINE EYE EXAM
  • IOP 19 MM HG OU
  • HX STROKE

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FUNCTIONAL COMPROMISE

  • INCONGRUOUS HOMONYMOUS HEMIANOPSIA NOT CONSISTENT WITH RNFL AND GCC THINNING
  • NEUROLOGICAL EVENT

ANALYSIS

  • PALE DISCS
  • RNFL DEPRESSION
  • GCC THINNING
  • RIGHT INCONGRUOUS HOMONYMOUS HEMIANOPSIA

OCULAR STRUCTURE COMPROMISE DOES NOT MATCH FUNCTIONAL COMPROMISE

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STRUCTURAL COMPROMISE

  • PROGRESSIVE THINNING OF THE GANGLION CELL COMPLEX

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ANALYSIS

  • RECOMMEND FURTHER QUESTIONING. “OH I HAD LASER TO BOTH EYES AND FORGOT.”
  • FOUND THE YAG PIS UNDER THE LIDS.
  • STRUCTURAL DAMAGE TO OPTIC NERVE HEADS FROM MIXED MECHANISM GLAUCOMA
  • STRUCTURAL DAMAGE TO GCC FROM MIXED MECHANISM GLAUCOMA AND APPEARS TO BE PROGRESSING
  • FUNCTIONAL DAMAGE FROM NEUROLOGICAL EVENT


CASE

  • 66 YEAR-OLD
  • POSITIVE FAMILY HISTORY OF GLAUCOMA
  • MEDICAL HISTORY: HYPERTENSION, HYPERCHOLESTEROLEMIA
  • TREATMENT: COSOPT BID OU AND LUMIGAN QHS OU
  • IOP 15 MMHG OU
  • CCT 555 OD 554 OS
  • VA 20/20 OU

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ANALYSIS

  • STRUCTURAL LOSS
  • FUNCTIONAL COMPROMISE
  • STRUCTURE DOES NOT MATCH FUNCTION-TESTING


CASE

  • 78 YEAR-OLD NO FAMILY HISTORY OF GLAUCOMA
  • NO PAST MEDICAL HISTORY
  • TREATMENT: TRAVATAN QHS OU
  • IOP 14 MMHG OU
  • CCT: 530 OD, 543 OS
  • VA: 20/20 OU

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ANALYSIS

  • “NORMAL” VISUAL FIELDS OU
  • SUPERIOR GCC LOSS AND RNFL LOSS OU
  • 3-D OPTIC DISC VIEW REVEALS SUPERIOR RIM NARROWING OU
  • CORRELATION OF SUPERIOR STRUCTURAL DAMAGE RESULTS IN PRE-PERIMETRIC GLAUCOMA DIAGNOSIS
  • STRUCTURE BEFORE FUNCTION


CASE

  • 35 YEAR OLD WHITE FEMALE
  • 14 YEAR HISTORY OF DIABETES WITH HEMOGLOBIN A1C OF 6.4
  • BEST VA OF 20/20 O.U.
  • NORMAL IOP NOT BEING TREATED FOR GLAUCOMA

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ANALYSIS

  • GOOD STRUCTURE/FUNCTION CORRELATION (SUPERIOR GCC & RNFL LOSS WITH INFERIOR VF LOSS)
  • SMALL OPTIC DISC WITH COMPLETE SUPERIOR STRUCTURAL LOSS SYMMETRICAL IN BOTH EYES
  • THIS CASE HAS SEVERE LOSS OF STRUCTURE AND FUNCTION SECONDARY TO DEVELOPMENTAL ISSUES: CONGENITAL
  • DX: SUPERIOR SEGMENTAL OPTIC NERVE HYPOPLASIA (“TOPLESS DISC”)


CASE

  • 60 YEAR OLD
  • PRESENTS FOR COMPREHENSIVE EXAMINATION
  • OCULAR HISTORY- NEGATIVE
  • MEDICAL HISTORY- GOUT, BORDERLINE HTN
  • MEDICATIONS- COLCHICINE, ALLOPURINOL
  • VA 20/20 OU
  • PUPILS- ? MG PUPIL OD
  • TA 29/28

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ANALYSIS

  • STRUCTURAL DAMAGE
  • CENTRAL CORNEAL THICKNESS NORMAL RANGE
  • FUNCTIONAL DAMAGE NOT VALID SECONDARY TO FIXATION LOSSES

GANGLION CELL COMPROMISE IN CONDITIONS OTHER THAN GLAUCOMA


PLAQUENIL

CASE

  • 54 YEAR OLD
  • ROUTINE EYE EXAM
  • DRY GRITTY EYES
  • HX SLE AND MEDS INCLUDE: ALEVE, PREMARIN, PROTEINEX, AND PLAQUENIL
  • BCVA 20/20 OU

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QUANTIFICATION OF STRUCTURAL CHANGES

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QUANTIFICATION OF FUNCTIONAL CHANGES

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ANALYSIS

  • NO FUNCTIONAL DEFECT MEASURED
  • STRUCTURAL COMPROMISE IN THE FORM OF PERIFOVEAL GCC/RETINAL THINNING

BRANCH RETINAL ARTERY OCCLUSION

CASE

  • 63 YEAR OLD
  • COMPLAINT OF REDUCED VISION OD
  • BCVA 20/40 OD 20/20 OS
  • IOP NORMAL RANGE

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QUANTIFICATION OF STRUCTURAL CHANGES

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INNER RETINAL THINNING = GANGLION CELL COMPLEX THINNING.

THE GCC IS JUST SLIGHTLY TEMPORALIZED IN THE MEASUREMENT.

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About the Author(s)

Larry J Alexander OD FAAO

Larry J Alexander OD FAAO

Dr. Alexander (1948-2016) was a 1971 graduate of Indiana University School of Optometry. He served in the US Navy then served as a Professor at the University of Alabama Birmingham School of Optometry. Larry contributed to a number of chapters in textbooks and has published three editions of Primary Care of the Posterior Segment, as well as contributed to the professional literature. He also lectured extensively in the area of ocular and systemic disease. His areas of special interest included dysfunctional tear syndrome, glaucoma and macular degeneration.  His lessons are the basis for this site and he will be dearly missed. 

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