Diagnostic Considerations in Contemporary Glaucoma Management COPE - 46913-GL C. Lievens, OD MS FAAO

US Glaucoma Statistics One of the leading causes of blindness in the US Over 4 million Americans have glaucoma 50% do not know they have it Approximately 5-10 million have elevated IOP Glaucoma ophthalmic drug therapy in 2011 was $3B By 2050, rate of glaucoma expected to triple US regions most likely: South & Southwest

Impact of Glaucoma What is the impact of vision loss (Va <20/40)? Increased risk of falls Hip fractures Depression Loss of social independence Reference 1. Taylor HR. LXIII Edward Jackson Memorial Lecture: Eye care: dollars and sense. Am J Ophthalmol. 2007;143:1-8. Taylor HR. Am J Ophthalmol. 2007;143:1-8.

Purpose of VF Testing To quantify functional ability in terms of the weakest spot of light (visual stimulus) that can be seen at representative locations in the visual field. Many factors need to be considered in the process.

Diagnostic Tests Gonioscopy 92020 Threshold Perimetry 92083 Ophthalmoscopy (Ext. 92225/6) Tonometry Random test Serial/diurnal measurement 92100 HRT/GdX/OCT/Talia/Optoview/etc. (ONH) 92133 Pachymetry 76514 Fundus Photography 92250 (ONH)

Visual Field Testing

What are we trying to measure with static perimetric testing?

Factors that Influence VF measurement

The “normal” visual field will vary for a given individual and between individuals Contrast between object and background VF testing is simply a measure of CSF Age Miosis Media clarity Uncorrected refractive error Perimetrist (not as much of a factor in automated testing, but worth the investment of training your staff!)

PERIMETRIST Important variable when considering results Prior to mid 80’s – performed manually by technicians perimetrist and patient variability Standardized Automated Perimetry (SAP) Eliminated some technician bias BUT still room for improvement “ the single most fertile areas for improving clinical perimetry – the management of and training of patients and technical staff. - Heiijl, et al (2012)

Released October 2012 “…Chapter 2 is particularly important because it explains how the perimetrist can improve test results even when using a highly automated instrument. The perimetrist should not simply stand by and watch the test, but should perform the test using the instrument….” Douglas R. Anderson, MD, FARVO Professor Emeritus Bascom Palmer Eye Institute

Patient Factors Age Attention Speed of reaction Understanding of test procedures Fixation Learning Effects All factors must be considered when choosing a visual field testing strategy

Interpretation of the VF results Correct interpretation of the results must analyze the field in terms of: Reliability Visual defect present Size and shape Location Density Repeatability

What are we trying to evaluate? GLAUCOMA NEUROLOGICAL CONDITIONS RETINAL DISORDERS OTHER

Review of landmark study results

AGIS AGIS (Advanced Glaucoma Intervention Study) 591 pts, 789 eyes Known pts with unstable VF and/or ONH’s Randomized trial to compare laser first surgery first Main result: No difference

AGIS cont. Important finding: Eyes with 100% of visits with IOP <18mmHg over 6 years had a VF defect score (from baseline) close to zero Important finding: Eyes with 50% of visits with IOP <18mmHg over 6 years showed VF progression

AGIS cont. IOP 18mmHg slowed progression 15mmHg showed ½ the progression of 18mmHg 13mmHg showed ½ the progression of 15mmHg Diurnals Important! Avg IOP = 15mmHg Curve 13-17 progresses less than 11-19

CIGTS (Collaborative Initial Glaucoma Treatment Study) 607 newly dx’ed pts Randomized to medical tx or trab. Medical IOP lowering of 35% Surgical IOP lowering of 47% VF is primary outcome observed 5-year outcome: No difference in patient quality of life

CNTGS (Collaborative Normal Tension Glaucoma Study) 145 eyes randomized Observation or 30% IOP lowering Using any drops, ALT, or trab 10 IOP readings – none>24mmHg Outcome 80% observation group progressed at 5 years 40% treated eyes progressed at 5 years

EMGT (Early Manifest Glaucoma Trial) Compare effect of: IOP tx NO tx Delayed tx 50-80 y/o’s POAG, NTG, Exfoliative Mild to moderate VF defects IOP > 30 or severe VF defects excluded

EMGT cont. 255 new patients Randomized to: 3mo f/u for 10 years ALT Betoptic Observation 3mo f/u for 10 years IOP reduced by average of 25% in treatment groups

EMGT cont. 45% progressed in tx groups 62% progressed in observation group Tx group progression @ 66 months Observe group progression @ 48 months Each 1mm of decrease related to 10% decrease of risk of progression

OHTS (Ocular Hypertension Treatment Study) Prospective study, 40-80 y/o’s 1636 patients randomized to 20% IOP lowering/24mmHg or observation IOP between 21-32 Normal SLE, ONH’s, VF 50% treated

OHTS cont. Results Lowering IOP by 20% reduces risk by 50% over 5 years Need to treat 100 people per year to prevent 1 from getting GLC

OHTS cont. Risk Factors identified Age: 22% increased risk per decade Race (African-American) Higher initial IOP: 10% increased risk per 1mmHg Thinner corneas Larger C/D’s: 32% increased risk with 0.1 increase Heart disease

Pachymetry Can be billed ONE TIME 36% of pts with IOP>25.75 & CCT<555 dx GLC 6% pf pts with IOP>25.75 & CCT>588 dx GLC 15% of pts with C/D .3rnd & CCT<555 dx GLC 4% of pts with C/D .3rnd & CCT >588 dx GLC

Corneal Thickness Take great care in using “pachymetry/IOP correction tables” OHTN Patients with thin corneas (<555 microns) were found to have a significantly greater risk of developing glaucoma then those with thick corneas (>588 microns )

CCT Powerful Predictor for the development of POAG Relative risk of POAG increased 81% for every 40µ thinner

Visual Field Analysis

Navigating the Print Map

The Visual Field Printout What does it tell you?? 1.) I.D. of patient and test 2.) Test Reliability 3.) Unprocessed Threshold Sensitivity 4.) Total Deviation-Measured v. Norm 5.) Pattern Deviation-Norm v. Pt performance after adjustment for overall sensitivity change 6.) Global Indices 7.) Gaze Tracking 8.) GHT – Plain Language Analysis

Raw Data Threshold points are plotted in db Normal central values will range around 30db ‘0’ means that a point was seen only at the brightest intensity Point not seen is marked ‘<0’

Gray scale Provides an approximate picture of the field. This should not be used in the analysis of the field

HFA Specific Reliablility indices Found in the upper left hand corner of the printout Fixation losses : FL False positive errors: FP False negative errors: FN

False positive Refers to the number of times a patient responds and no target is presented. Flagged if it exceeds 33% May be a sign of a “trigger happy” patient and will artificially improve the VF

False Negative Refers to the number of times a patient fails to respond to a suprathreshold target placed in a seeing area of the visual field. Flagged if it exceeds 33%

Total Deviation Plot (db) Appears as numbers and graphic in the central left area of printout Represents the difference between the measured threshold of each individual test location and the age-corrected normal value for that location

Pattern Deviation Plot (db) Takes the Total Deviation plot and adjusts it upwards or downwards to screen out generalized depression

Probability Plots (p value) Found in between gray scale of total deviation and pattern deviation plots Indicates how frequently a total or pattern deviation value at a particular test location is found in the normal population

Global indices Found on the lower right hand corner of the printout Visual Field Index (VFI) Mean deviation (MD) Pattern standard deviation (PSD)

Visual Field Index Recently developed staging index to assist in separating changes in overall depression of field due to media opacity. Provides improved correspondence to ganglion cell loss compared to Mean Deviation alone. RANGE 100% (normal) to 0% perimetrically blind eyes

Mean Deviation (MD) Average departure (+ or -) of each test location from the age-corrected normal value Can be affected by overall depression as well as significant loss in one part of the field.

Pattern Standard Deviation (PSD) Measures the extent to which the threshold determinants at different locations differ from each other Very significant indicator of field abnormality, especially if p < 5%

Interpretation of the Global Indices Mean Deviation PSD Interpretation Normal Visual Field probably normal Abnormal Generalized loss of sensitivity Small localized defect Large defect with a localized component

Pharmacology comparison XLT Study: (Xalatan vs. Lumigan vs. Travatan) Summary No racial difference between racial groups were noted Subjective Fewer patients had claims of ocular hyperemia with latanaprost (researchers agreed) Note subsequent study agreed and added the same conclusion with eyelash growth

Pharmacology comparison Ocular and systemic side effects of Alphagan .2% in children There have been occasional reports of systemic adverse effects in children including apparent central nervous system depression. There are few data available on the overall safety of brimonidine 0.2% in children. In this study, 18% of children had systemic adverse effects sufficient to necessitate stopping the drug

Alphagan P in Peds??? Still NOT recommended Report severe breathing problems with use in children under age 2 Take caution

Severity of Glaucoma Mild Moderate Severe characteristic optic nerve abnormalities are consistent with glaucoma, but there is a normal visual field. Moderate visual field abnormalities are in one hemifield and not within 5 degrees of fixation. Severe visual field abnormalities are in both hemifields or loss is within 5 degrees of fixation.

Glaucomatous optic nerve changes Asymmetric C/D ratios Optic cupping Vertical cup elongation Notching / temporal unfolding Shifting of disc vessels Saucerization of the cup Bean-potting Visible lamina Optic nerve collateral development Peripapillary atrophy Neuroretinal rim loss Optic disc hemorrhages Nerve fiber layer loss Cup-pallor discrepancy

Targeting IOP Cookbook Initial target: reduce by 20-30% From highest IOP Mild GLC 20-30% Moderate GLC 30-40% Severe GLC 40-50+%

Patterns and Progression Glaucomatous VF Loss Patterns and Progression

Patterns of Visual Field Loss Glaucomatous VF Loss Generalized Depression Diffuse loss of retinal sensitivity Increased variability Asymmetric superior/inferior VF Focal VF Loss Arcuate scotoma or Bjerrum scotoma Altitudinal defect Paracentral scotoma Early and Later Nasal Step Patterns of Visual Field Loss

Loss of Temporal Island Glaucomatous VF Loss Generalized Focal/Localized Early defects Late Defects ADVANCED VF LOSS Central Field with Temporal Island Splitting of Fixation Loss of Central Field Loss of Temporal Island Patterns of Advancing Focal Visual Field Loss

Location, Location, Location 63% above horizontal 7% show initial field defects outside 30° with normal central fields Optic Nerve Evaluation in key! With analysis of risk factors, IOP and CCT

Analysis of the VF Print-out Comparison analysis can identify the earliest generalized depressions Inter-eye differences: MD, quadrant dB Hemifield comparison: point to point on horizontal midline Multiple field symmetry: point to point between tests

Improving Compliance G. Swartz, Improving Patient’s Adherence to Glaucoma Therapy, Glaucoma Today, Spring 2011, 53-54.

Glaucoma Adherence & Persistance Study (GAPS) N=~14K Pharmacy claims data Patient chart review Doctor interviews Patient interviews

Common barriers to compliance: Concern about side effects (67%) Difficulty with eye drops (36%) Cost (25%)

Factors associated with nonadherence Does not connect nonadherence with vision loss Exclusive dependence on the doctor for information and education Cost Race Sampling

Recommendations

Ask questions effectively Non-judgemental Inquire about difficulties Cost Running out Side effects Forgetfulness Drop adminstration

Find out what patients know Ask patients to state their understanding of glaucoma and the benefit of using drops

Learn about missed doses Ask patients how many times per week or month they have missed their medications Simplify the dosing regimen as much as possible Link the dosing whenever possible to a daily part of a routine Be sensitive to economics

This study shows that in a group of stable open angle glaucoma patients, the addition of home tonometry performed using Proview as an adjunct to their IOP lowering medication did not have any significant effect on the amount of medication used, thus compliance was not significantly affected.

Why? First, using once-a-day medications patients may already at the maximum state of compliance by their very nature. The addition of Proview usage could have distracted a percentage of them in the same way that an additional medication would.

Why? Secondly, “good” Proview readings may have lured them into a false sense of security. Patients may have consciously decided to halt their medications on “good” IOP days. all patients were aware of their target IOP

Interobserver Reliability

Interobserver error is of concern Even with experts, the vertical C/D measure has been proposed to lack clinical usefulness (with differences of 0.2 disk diameters (DD) or more between individual observers being commonplace).

Optometry Research has found glaucoma trained fellows to be superior in grading C/D ratios as compared to optometry and general ophthalmology. Specifically interobserver agreement in estimating C/D was significantly higher for GLC Fellows when compared to optometrists, residents, and general ophthalmologists

Why? It has been reported that 41% of surveyed eye care practitioners have no method that they consciously use to gauge C/D ratios, except experienced estimation.

Results The use of our card places both optometrists and interns in the substantial agreement category (as were glaucoma specialists)