James Thimons, O.D, FAAO

Dr. Thimons is a 1978 graduate of Ohio State University College of Optometry. He

completed his hospital residency at the Chillicothe, VA Medical Center in 1979 and then

served as Chief, Optometry Service until 1985. He then accepted the position of Center

Director at Omni Eye Services, Fairfax, Virginia and served in that role until 1989 when

he became Chairman, Department of Clinical Sciences. While at SUNY he developed

The Glaucoma Institute at the State University of New York, a glaucoma clinical research

center, and served as its first Director. In 1998, he accepted the position of Executive

Director of TLC and served in that role until 2002 when he co- founded Ophthalmic

Consultants of Connecticut. A multidisciplinary referral practice providing secondary and

tertiary level care! Dr. Thimons has received numerous awards for his service to the

profession and has over 200 hundred publications in the area of ocular disease

management. He is a nationally and internationally acclaimed Speaker and Educator and

an acknowledged leader in ophthalmic clinical education. He serves in professorial

appointments at several universities in the US and has been a clinical investigator in over

20 NIH, NEI and Post Release Clinical Trials. In 1999 he was awarded Optometry’s Top

Educator and was selected as one of the Top Ten ODs of the decade. In 2002 he founded

the National Glaucoma Society, a NFP with Executive offices in Andover,

Massachusetts, that provides educational and clinical development services to primary

care clinicians worldwide in the area of glaucoma. In 2005 he was inducted into the

Optometry Hall of Fame and has recently served as President, Connecticut Association of

Optometrists.

9/24/2013

1

Clinical Update 2013J. James Thimons, O.D.,FAAOClinical Professor/ PCOFounding Partner/ Ophthalmic Consultants of Connecticut

Not A Dry Eye in The HouseSAR 1118 ( Lifitegrast/ SARcode Bioscience, Brisbane , CAL.)Phase III / OPUS-I Trial588 patients /13 sitesBID dosing ( Drug vs. Placebo)T-cell modulatorLymphocyte function-associated antigen LFA-1 inhibitor of ICAM-I ( Prevents activation of

T cells which mediate inflammation)Blocks active T-Lymphocytes vs inhibiting new cell development ( 100-110 day full

inflammation cycle)Faster action/increased efficacy vs. RestasisClinical trials show 2 weeks to onset of action

A New View on OM3’sResolvin ( Resolvyx Pharmaceuticals, Cambridge, Mass)“Super Fish Oil”10,000 x more potent than oral fish oils?Phase II completed

Another Oral FQ RiskBritish Columbia Eye Center 2012

– BC Ministry of Health database4.384 patients RD43,840 healthy matched controlsFQ use concurrent with RD 5.5x greater riskAdjusted data ( cataract Sx, myopia etc ) 4.5xFQ use in preceding 12 months 1.55x

Chemical Vitrectomy: The Next Step in VMT Management Ocriplasmin ( ThromboGenics)

– Two Phase III MIVI-TRUST studies266 patients with VMT treated with a single 125 ug dose of intravitreal therapy29.8% of treated patients resolved vs. 7.7% of placebo at day 28153 patients with macular hole showed a 60% resolution at day 28 vs. 16% placeboMacular holes between 250-400 um showed 36.8% vs. 5.3% in placeboMacular holes greater than 400 um showed no resolution

1

2

3

4

5

6

9/24/2013

2

Glaucoma: Not Just a Goal PressureJour. Of Glaucoma 201241 glaucoma patients / mean age 7022% had some degree of cognitive impairment vs 16% in age matched populationTesting done with:

– California Verbal Learning Test– Delis-Kaplan Executive Function System

Direct affect on compliance

Habla Espanol Anyone?AJO 20123,909 patients/ mean age 54.7POAG/ OHTN4 year POAG data shows 2.3% vs. 1.1% with non-Hispanic whites4 year OHTN data shows 3.5%Unilateral POAG showed 5x greater risk of second eye at 4 yearsUnilateral OHTN showed 10x greater at 4 years

Can There be Too much Prostaglandin?Alverado, J; Oct 2009 UCSFLaboratory Analysis of Effect of SLT on Trabecular OutflowSCE’s were exposed to six different IOP lowering drugs and SLT/TME’sThe junction assembly/dissassembly was monitored by confocal flourescent time lapse

microscopyLatanaprost, bimatoprost & Travaprost shared a common mechanism of action with SLT

– Widening of the paracellular pathways– Induction of intercellular junction dissassembly– Decreased transepithelial flow across SCE’s

Clinical impact: TME’s play a critical role in regulating SCE’sNon-Competing IOP agents may improve IOP spot SLT

There is Sleep at the End of the Day!Johansson K; BMJ: 200963 obese malesBMI 30-40/ age 30-65Moderate –Severe Sleep Apnea treated with CPAP30 assigned to low energy liquid diet x7 weeks, then two weeks of normal diet/ others

maintained usual diet x9 weeksIntervention group 20kg lessAHI’s decreased 20/hour5 became disease free/ 15 reduced to mild OSANo change status in non intervention group.

Two Halves are worse than One!

7

8

9

10

11

9/24/2013

3

Arch Ophthalmol; 2009205 eyes of 205 patients with glaucomatous optic neuropathyMinimum 10 QVF’s over 5 years < 6dB3 groups;

– 79 with initial superior defect– 61 with initial inferior defect– 65 with both hemifields

Mean follow up was 6.5 yearsGroup C had most rapid progression

iStent (Glaukos)

Why Trabecular Bypass Surgery?Stent / Efficacy:Schlemm’s canal is part of the aqueous outflow pathwayiStent® restores aqueous outflow chain by bypassing only the blockage that occurs with

glaucoma in the trabecular meshworkIOP reductions to mid teens

Glaukos Efficacy

Glaukos AdvantagesQuick to performNo dependence on prior proceduresMay be able to titrate with multiple procedures

Glaukos DisadvantagesVery low IOPs not likelyNeed open anglePlacement of earlier device is sometimes difficult

Take Your Time: It’s Worth it!Fraunfelder, FW et al: Cornea 201012 subjects/ failed on initial therapy of lubrication/ NaClTreated with bandage lens x 3 months 75 % had complete resolution at one year from initial Tx2 had symptoms but no signs1 patient had symptoms and signs

I Just Wanted to Lose a Few Pounds!Jour. of Gastrointestinal Surgery 2004Assessed Vitamin A deficiency in post Bariatric surgery patients1 year 50% of bypass patients were Vitamin A deficient4 years 70%Ocular complications:

– Mild- Dry Eye – Severe- Bitot’s Spots/ Xerophthalmia/ Nyctalopia

12

13

14

15

16

17

18

9/24/2013

4

Tx: Dependent on severity– Oral supplementation 5000mg po qd– IM injection 20,000 IU’s x 2-3 weeks– Restasis bid OU / 1% initially then standard concentration

–

Amantadine: A Very Unexpected OutcomeWelder J; et al: EyeRounds.org 2010Case report on corneal edema associated with Amantadine use.Severe endothelial cell loss OUPachs: 890/900Minimally response to PFChang et al postulate etiology as direct endothelial toxicityOccasionally reversible if early in disease.

DSEK & Glaucoma: The Real TruthOphth 2012Five year graft survival rates in medical vs: surgical management553 DSEK eyes

– 438 no glaucoma– 65 medical management– 46 surgical management

96% graft survival in non-glaucoma group90% in medical management group48% in surgical group

– 25% with drainage device– 59% with trabeculectomy

Fourth Generation FQ’s & DiplopiaOphthalmology; Sept. 2009; Oregon Health Sciences171 cases of diplopia associated with FQ use 76 men/ 91 women/ 4 non-genderMedian dose was wwnl for package insert recommendationsMedian time to onset 9.6 daysMeds d/c in 53 patients all resolvedWHO rating: PossibleMechanism? Tendinitis of the EOM

Another Look at MRSA!Asbell, P; Topics in Ocular AntiinfectivesOcular TRUST II 2008 ( Tracking Resistance in United States Today)155 ocular isolates in US sent to reference labs for centralized in vitro testing84/155 ( 54%) were Methicillin resistant compared to Ocular TRUST I 2005 data which

showed predominant response to be Methicillin sensitive.MSSA Sensitivities:

– Trimethoprim 97%– Tobramycin 95%– FQ’s 93%

19

20

21

22

9/24/2013

5

– Azithromycin 62%MRSA Sensitivities:

– Trimethoprim 95%– FQ’s 18%– Tobraymycin 50%– Azithromycin 8%

Strep P. Sensitivities– FQ’s 100%– Trimethoprim 80%– Tobramycin 2%

H Flu SensitivitiesAll drugs 100% except Trimethoprim @ 85%

––

TearScience® Solution

LipiView® Output

Interferometric Color Unit (ICU) statistics calculated on a frame-by-frame basis and processed for ~ 1 billion data points per eye.

The results are displayed and available for printout.

–

Normal Meibomian Glands

Non-Obvious MGD

LipiFlow® Thermal Pulsation System

Overall Therapeutic Goal of the LipiFlow®Alleviate meibomian gland obstruction in both upper and lower eyelids simultaneously,

using a short in-office procedure (12 minutes per eye)

Therapeutic Goal of PulsationTransiently decrease blood flow to the tissue surrounding the glands, thus increasing heat

transfer efficiencyEvacuate liquefied gland contents to alleviate the obstructionCause less eyelid discomfort or pain as compared to manual gland expression

Loteprednol to the RescueCornea, 2009

23

24

25

26

27

28

29

30

31

9/24/2013

6

15 month retrospective review of PK patients switched from Pred Forte to loteprednol30 patients initiated Loteprednol after IOP spikeMean reduction of 12.9 mmHg:

– 32 % at 3 weeks– 44.9% at 6 weeks

All grafts were maintained with rejection

One More Vote for RestasisCornea 2009

– 13 PATIENTS WITH Graft vs: Host disease– 9 patients with Primary or Secondary Sjogren’s– Prior bid dose was 6 months– Increased dose at qid

68% showed significant improvement at 2 monthsCorneal/ Conjunctival staining showed a 3.5 points from baseline imporvement G vs HA 2.8 points improvement in Sjogren’s Limitations: Small sample size

–

Tracking the Elusive Diurnal!Sensimed: Swiss medical device company. Jean Marc Wismer CEODevice is called TriggerefishTracks fluid pressure in the eye and beams data to palm size recorder. Uses a circular antenna taped around the eye and connected to a battery powered

portable recorder.This transmits radio frequency energy to an utlra thin gold ring in the CL. This powers a

chip embedded in the lens.Additionally on the lens in an ultra thin platinum ring that stretches in response in variation

in eye shape secondary to pressure.Available in Europe. Primary trial at University Hospitals of Geneva

Are You Looking at Me?He J, et al: Zhongsan Ophthalmic Center Eye 2004339 patients /597 eyes with Thyroid Associated Ophthalmopathy (TAO)OHT incidence was 31.3 %/ greater in malesMechanism was compression of globe by EOM’s Increased in upgaze

Punctal Plugs with Latanoprost CoreQLT, Inc44-g Latanaprost Punctal Plug Delivery SystemPhase IIData:

– Mean change form baseline -3.5 mmHg– 36% showed reduction of >/= 5mmHg– Overall goal of 90% retention/ Initial 75%– Second generation plug 90%– Goal of therapy 90 days of Tx

32

33

34

35

9/24/2013

7

Glaucoma & PregnancyBJO 2009; JD Ho: 244 pregnant women treated for glaucoma analyzed for birth weight1,952 age matched controlsNo significant difference between women on BB’s vs: no TxHerndon, L: D/C Brimonodine several weeks before d/t risk of apnea

SLT on the Rise!Journal Glaucoma 2012 KatzProspective multicenter trialof 127 eyes of 69 patientsMedical vs: SLT

– Mean IOP medical 24.7mmHg– Mean IOP SLT 24.5 mmHg

Six follow up visits over one year– SLT 18.2 mmHg ( 6.3 reduction)– Medical 17.7 mmHg ( 7.0 reduction)

11% of eyes required SLT retreatment27% of eyes required additional medsStudy enrollment limited to early to moderate disease

RAPDX : UNDERSTANDING THE OPTIC NERVE IN GLAUCOMA

RAPDx Expanded Pupil DiagnosticsAutomated pupillographyDesigned to detect a relative afferent pupillary defect (RAPD)Assessment of differential amplitudes and latenciesObjective test of visual pathway functionTest time is 1 to 5 minutes

Relative Afferent Pupillary DefectRelative afferent pupillary defect (RAPD) is an asymmetry in the pupillary light responseDetection of RAPD is performed by alternately illuminating each eye while comparing the

velocity and amplitude of the pupillary responsesNeutral density filters in 0.3 logarithmic unit steps aid in the detection and quantification of

RAPDThe size of the RAPD can be quantified by he density of the neutral density filter required

to balance the response of each eye

Clinical Benefits of RAPDx TestingRAPDx technology represents a paradigm shift in pupil testingRemarkable sensitivity for detecting glaucoma

– Sensitivity = 81%– Specificity = 90%

By comparison, IOP has a 65% sensitivity for detecting glaucomaRAPDx results correlate with VF and RNFL tests

–

Case Report

36

37

38

39

40

41

42

9/24/2013

8

Optical Coherence TomographySevere fallout of the retinal nerve fiber layer in the left eyeAbnormal TSNIT curve profile analysisAbnormal sector plot analysisAbnormal symmetryOCT test results are consistent with glaucoma

Visual Field Examination

RAPDx Pupillary Testing – Amplitude

RAPDx Pupillary Testing – Latency

Epidemic KeratoconjunctivitisEKC

– Serotypes 8,19 most typical– Seasonal – Primarily bilateral– Atypical serotypes; Enterovirus 70

Clinical Presentation– Chemosis– Injection– Infiltrates– Ac/reaction?– FBS–

EKCTreatments

– PalliativeCold compressTears

– InterventionalAnti-inflammatory agentsDecongestantsCombination agentsCidofovirZirgan?

EKCTreatments

– Betadine wash– Surgical Debridement

43

44

45

46

47

48

49

50

51

52

9/24/2013

9

ZIRGAN®

(ganciclovir ophthalmic gel) 0.15%FDA approval 9/16/2009Available in Europe under the trade name Virgan (Laboratoires Théa) since 1996Purchased from Sirion by Bausch & Lomb 2010

Adenovirus Conjunctivitis and keratoconjunctivitis caused by adenoviruses are common and highly

contagiousUsually affect both eyes and may cause epidemicsPatients may have painful conjunctival membranes and palpable preauricular

adenotherapy Zirgan is active in vitro against adenovirus as1

Tabbara did a controlled randomized double-masked clinical study of patients with adenovirus keratoconjunctivitis and found that ganciclovir significantly reduced both the duration of disease and the incidence of subepithelial infiltrates2

Adenovirus clinical trial (Tabbara, 2001)Controlled randomized masked series of 18 patients with adenoviral keratoconjunctivitis Compared treatment with GCV ophthalmic gel 0.15% versus preservative-free artificial

tearsMean time to recovery Significantly shorter for ganciclovir-treated patients: 7.7 days, in contrast to 18.5 days

for those receiving artificial tears (P < 0.05) Subepithelial opacities Developed in 7 (77%) patients treated with artificial tears, compared to 2 (22%)

patients in the GCV-treated group.

Floppy Eyelid Syndrome

Classic PatientMale age 30-70Overweight or obeseChronic irritation, tearing, redness, dischargeProblem worse on the side on which he sleeps

Physical FindingsLoss of rigidity of tarsal plateEasy eversion of lidPtosisLash Ptosis

53

54

55

56

57

58

59

60

61

9/24/2013

10

Chronic conjunctival changesChronic corneal changes

PathophysiologyPathology studies disclosed decreased elastin within tarsal plate and eyelid skinIs this due to chronic mechanical irritation or is it the cause of the problem?

Role of Eye RubbingAnecdotal association with keratoconusUnknown contribution of repeated mechanical irritation of the eyelid

Pathophysiology of Signs/SymptomsPRIMARY:

– Repeated eversion of lid during sleep abrades conjunctiva and cornea on beddingSECONDARY:

– “Rough” conjunctiva abrades bulbar surface and cornea– Distracted lid unable to blink tears across eye– Ptotic lashes +/- lid blocks superior vision–

Management Options1. Conservative

-Eye shield to the affected side at bedtime(approximately 1/3rd of patients may be sufficiently treated by a shield alone)

-Nightly ointment

2. Surgical-Various methods of eyelid tightening procedures

Surgery for FESClassic Approach = Eyelid tightening:

– Wedge excision– Lateral tarsal strip– Medial plication

Disadvantage:– Lid continues to have tendency to evert and stretch over time– High reoperation rate

AMD & RPE: A Marriage MadeOphth 2102108 patients in Placebo controlled trial of lutien & Zeaxanthin of macular pigment optical

density– Group 1 placebo– Group 2 10mg – Group 3 20 mg lutein– Group 4 10 mg lutein/ 10 mg zeaxanthin

MPD change correlated directly with Luteindosage.

62

63

3

64

65

66

67

9/24/2013

11

No change in visual function ( snellen, contrast, amsler or photoreceptorrecovery) was observed

OHTN and CCT• Falsely elevated intraocular pressure due to increased central corneal thickness. Graefes

Arch Clin Exp Ophthalmol. 1999 Mar;237(3):220-4• 48 OHTN subjects - 592+/-39• 63 patients with POAG 536+/-34• 106 normal subjects 545+/-33•• Relationship between corneal thickness and measured intraocular pressure in a general

ophthalmology clinic. Ophthalmology. 1999 Nov;106(11):2154-60• 232 OHTN subjects – 579.5• 335 patients with POAG 550.1• 235 normal subjects 545+/-33• 52 Normal-tension glaucoma 514•

Goldmann ApplanationThe Gold standard in IOP measurement for 50 yearsGoldmann & Schmidt : when tonometer head is 3.06 mm in diameter and there is a

normal central corneal thickness of 500 microns – surface tension = corneal rigidityCCT is relatively constant in the absence of corneal disease

CCT as a risk factor in patients with glaucomaAnalysis of 350 eyes of 190 patients with POAG during initial visit to specialist.

• In multivariate analysis, lower CCT was significantly associated with worsened AGIS score, worsened mean deviation of visual field, and increased vertical and horizontal cup-disc ratios.

• Herndon et al. Central corneal thickness as a risk factor for advanced glaucoma damage. Arch Ophthalmol. 2004 Jan;122(1):17-21

•

ORA Signal Analysis

Corneal Hysteresis

Corneal-Compensated IOP (IOPCC)

Frequency Distribution: CCT

68

69

70

71

72

73

74

75

76

77

78

79

9/24/2013

1

Glaucoma – RNFL Thickness Analysis

Cirrus Software Version 6.0New insights from the cube and more!

Ganglion Cell AnalysisMeasures thickness for the sum of the ganglion cell layer and inner plexiform layer (GCL + IPL layers) using data from the Macular 200 x 200or 512 x 128 cube scan patterns.RNFL distribution in the macula depends on individual anatomy, while the GCL+IPL appears regular and elliptical for most normals. Thus, deviations from normal are more easily appreciated in the thickness map by the practitioner, and arcuate defects seen in the deviation map may be less likely to be due to anatomical variations.

Ganglion Cell Analysis

Ganglion Cell Analysis

Updated Guided Progression Analysis (GPA™)Optic Nerve Head information now includedAverage Cup-to-Disc Ratio plotted on graph with rate of change information.RNFL/ONH Summary includes item “Average Cup-to-Disc Progression”.Printout includes an optional second page with table of values, including Rim Area, Disc Area, Average & Vertical Cup-to-Disc Ratio and Cup Volume. Each cell of the table can be color coded if change is detected.Miscellaneous updates to the report design.

Updated Guided Progression Analysis (GPA™)

RAPDX : UNDERSTANDING THE OPTIC NERVE IN GLAUCOMA

RAPDx Expanded Pupil DiagnosticsAutomated pupillographyDesigned to detect a relative afferent pupillary defect (RAPD)Assessment of differential amplitudes and latenciesObjective test of visual pathway functionTest time is 1 to 5 minutes

Relative Afferent Pupillary DefectRelative afferent pupillary defect (RAPD) is an asymmetry in the pupillary light responseDetection of RAPD is performed by alternately illuminating each eye while comparing the

velocity and amplitude of the pupillary responsesNeutral density filters in 0.3 logarithmic unit steps aid in the detection and quantification

1

2

3

4

5

6

7

8

9

10

11

12

9/24/2013

2

of RAPDThe size of the RAPD can be quantified by he density of the neutral density filter required

to balance the response of each eye

Eye Diseases that may lead to a RAPDGlaucoma: Even though glaucoma affects both eyes, if the disease is more severe in one

eye, a RAPD may be detectedRetinal Disease: Diabetic retinopathy, arterial occlusions, sickle-cell retinopathy, and

retinal detachments may produce a RAPDOptic Nerve Disease: Disorders such as optic neuritis are a common cause of RAPDNeurological Disease: Lesions of the midbrain, compressive lesions

Clinical Benefits of RAPDx TestingRAPDx technology represents a paradigm shift in pupil testingRemarkable sensitivity for detecting glaucoma

– Sensitivity = 81%– Specificity = 90%

By comparison, IOP has a 65% sensitivity for detecting glaucomaRAPDx results correlate with VF and RNFL tests

–

Case Report

Optical Coherence TomographySevere fallout of the retinal nerve fiber layer in the left eyeAbnormal TSNIT curve profile analysisAbnormal sector plot analysisAbnormal symmetryOCT test results are consistent with glaucoma

Visual Field Examination

RAPDx Pupillary Testing – Amplitude

RAPDx Pupillary Testing – Latency

Goldmann ApplanationThe Gold standard in IOP measurement for 50 yearsGoldmann & Schmidt : when tonometer head is 3.06 mm in diameter and there is a

normal central corneal thickness of 500 microns – surface tension = corneal rigidityCCT is relatively constant in the absence of corneal disease

OHTN and CCT• Falsely elevated intraocular pressure due to increased central corneal thickness. Graefes

Arch Clin Exp Ophthalmol. 1999 Mar;237(3):220-4• 48 OHTN subjects - 592+/-39• 63 patients with POAG 536+/-34• 106 normal subjects 545+/-33•

13

14

15

16

17

18

19

20

21

9/24/2013

3

• Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic. Ophthalmology. 1999 Nov;106(11):2154-60

• 232 OHTN subjects – 579.5• 335 patients with POAG 550.1• 235 normal subjects 545+/-33• 52 Normal-tension glaucoma 514•

CCT as a risk factor in patients with glaucomaAnalysis of 350 eyes of 190 patients with POAG during initial visit to specialist.

• In multivariate analysis, lower CCT was significantly associated with worsened AGIS score, worsened mean deviation of visual field, and increased vertical and horizontal cup-disc ratios.

• Herndon et al. Central corneal thickness as a risk factor for advanced glaucoma damage. Arch Ophthalmol. 2004 Jan;122(1):17-21

•

Canaloplasty

Effects of Suture Tension

Canaloplasty

Canaloplasty AdvantagesNon-invasiveNo destruction of anatomyHypotony unlikelyRapid recoveryHigh Safety Profile

Canaloplasty DisadvantagesLonger operating timesLearning curveSometimes cannot cannulateExtensive prior scarring may eliminate possibility of performing procedure

ORA Signal Analysis

22

23

24

25

26

27

28

29

30

31

32

33

34

35

9/24/2013

4

Corneal Hysteresis

Corneal Resistance Factor

Corneal-Compensated IOP (IOPCC)

Frequency Distribution: CCT

Frequency Distribution: CCT

What’s new with tonometry you ask?

New Icare tonometerNo anestheticNo disinfectionDisposable probe Touches the cornea for only a fraction of a second “Rebound Tonometry”Beneficial for difficult patients… children and those with dementiaBut is it accurate?

What about Pascal Dynamic Contour Tonometry• Pascal Dynamic Contour Tonometer is a new device that can measure 1. IOP 2. ocular pulse amplitude (OPA) which is the difference between diastolic IOP and systolic

IOP.••• OPA is suggestive of choroidal blood flow. • IOP measurements using Pascal Dynamic Contour Tonometer are less influenced by

corneal thickness as opposed to Goldmann applanation which measures higher values in thicker corneas

Pascal Dynamic Contour TonometrySlit-lamp-mounted - same easy operation as the familiar applanation tonometer. Convenient disposable tip prevents contamination and potential infection. Direct measurement of pressure - no systematic errors from force-to-pressure conversion. Numerical display of result - avoids operator bias and reading errors. No mechanical calibration required; self-calibrating. Battery operated - no cabling.

PASCAL offers valuable clinical benefits•• The PASCAL Dynamic Contour Tonometer (DCT) is a digital contact tonometer for

ophthalmological applications. The slitlamp mounted device furnishes a numeric output of

36

37

38

39

40

41

42

43

44

45

2

46

9/24/2013

5

intra-ocular pressure (IOP) and of ocular pulse amplitude (OPA) upon touching the cornea for a few seconds. It measures pulsatile IOP directly and continuously (dynamically).

• Unlike applanation tonometers which are influenced by corneal thickness and other characteristics of the cornea, and hence may produce misleading estimates of IOP, the PASCAL tonometer provides an accurate and direct measurement of true IOP, which is independent of inter-individual variations in corneal properties and biomechanics.

•• Note that IOP measurement is accurate even on post-LASIK and keratoconic eyes. •• PASCAL detects and accurately measures the dynamic fluctuations in IOP and thus allows

for a more detailed assessment of the pressure range to which the eye is subjected due to pulsatile ocular blood flow.

••• PASCAL repeatedly samples intraocular pressure at a rate of 100 times per second. The

ocular pulse amplitude (OPA) and the systemic pulse rate are continuously measured and recorded by the instrument. In addition, the ocular pressure pulse is graphically represented on the patient report.

•

How close are we to continuous 24 hour IOP measurement? Goldman tonometry snapshot in time of a very dynamic parameter that is IOPBody posture affects IOPMedications have a variable effect on IOPSmall group of POAG patients wore a Sensimed Triggerfish soft contact lens with an

embedded micro-electromechanical system that communicates via wirelessdynamic; 15 patients that showed progression, despite being “controlled” were monitored for 24

hours70% of cases showed highest values during the night—some treatments were altered

based on resultsCould this be the future?

Tired of trying to take pressures on this guy?

Diaton TonometerLimit of the admissible measurement error in the range, not more:

from 5 to 20 mm Hg - ±2 mm Hg;from 20 to 60 mm Hg - ±10%

Transpalpebral "diaton" tonometer is effective and irreplaceable in various situations:screening examinations of the patients IOP control during selection of adequate medicines IOP measuring in the presence in a patient of chronic conjunctivitis, erosions, edema and

cornea dimness IOP measuring in patients after corneal surgeries

IOP measuring in immobilized patients and in children

47

1

2

48

49

1

2

9/24/2013

6

IOP measuring during contact correction (lenses are not taken out).

Trabeculectomy with Express Minishunt

Express Minishunt AdvantagesReduces operating timeEyes appear to be quieter earlier in post-op courseNo iridectomyUniform openingIf hypotony occurs, tends to be less severe

Express Minishunt DisadvantagesNeeds some suturing as in trabeculectomyDependent on patient healingAnti- metabolites still routinely usedPatient has blebHypotony possible

Reasons to use the ExpressSimplify procedureShorten surgery timeDecrease tissue manipulationEliminate need for iridectomyDecrease chance of ostium obstructionRegulate flow in short termCreate less short term inflammation

Arguments AgainstExpenseForeign bodyMetal in eyeCorneal contact

Patient SelectionSame as trabeculectomyMay work better in high risk patients

50

51

52

53

54

55

56

57

58

59

60

61

62

9/24/2013

7

ICE patientsNV patientsShallow/synechiae

Resident Surgery with Ex-PRESSNo difference

– postoperative IOP– proportional decrease in IOP

Ex-PRESS group – Significantly less medication to control IOP at 3 months– No difference at 6 months or 1 year (P≥0.28)– More Ex-PRESS patients had good IOP control without meds at 3 (P=0.057) and 6

months (P=0.076)– No difference was found in the rates of sight-threatening complications (P≥0.22)

Retrospective Case SeriesFinal percent IOP lowering was similarMoorefields Bleb Grading System

– Less vascularity and height but more diffuse area associated with the Ex-PRESS blebsFewer cases of early postoperative hypotony and hyphemaQuicker visual recovery

– The Ex-PRESS group required fewer postoperative visits compared with the trabeculectomy group (P < .000).

5 year study Ex-press vs TrabeculoectomyEX-PRESS more effective without medication

– At year 1 12.8% of patients required IOP meds after EX-PRESS implantation vs 35.9% after trabeculectomy

– At year 5 (41% versus 53.9%) Responder rate was higher with EX-PRESSTime to failure was longerSurgical interventions for complications were fewer after EX-PRESS implantation

VEP in Glaucoma

LASERS

LASERSBy now we should all agree that lasers can be a first line treatment

63

64

65

66

67

68

69

70

71

72

73

74

75

76

9/24/2013

8

Shown to be as effective as drops in “Glaucoma Laser Trial”Since late 90’s SLT has slowly been replacing ALT as the laser of choiceIOP average lowering about 23% What’s new you ask?

MLT anyone?MicroPulse Laser TrabeculoplastyRecent study showed no difference between SLT and MLT on scanning electron

microscopy Micropulse laser trabeculoplasty (MLT) provides the same IOP-lowering effects as argon

laser trabeculoplasty (ALT) and selective laser trabeculoplasty (SLT) with less energy and inflammation than the earlier procedures.

MLT is performed with the 810-μm IQ 810 photocoagulator (Iridex, Mountain View, Calif.), a multipurpose ophthalmic laser that can be used for transpupillary, transcleraland intraocular treatments. The device treats the deeply pigmented cells of the trabecular meshwork (TM) through laser-induced thermal elevation.

ALT vs. MLTALT with a 50 micron spotMLT

QUANTEL MEDICAL Linear UBM

Ultrasound Biomicroscopy(UBM) of the eye

Visante™ OCT Anterior Segment Imaging and Biometry

MethodologyFill bag ¾ with tap water Add water slowly to minimize air bubblesLIN50 – USE DISTILLED WATER

Methodology (Preferred)

Clinical Applications

77

1

78

1

2

79

80

81

82

83

84

85

9/24/2013

9

Glaucoma (lights off exam)

Phakomorphic

PhakomorphicBulky ciliary body in phakomorphic angle closure

Pupil Blockbefore and after YAG laser

Plateau iris

Cyst

The Ganglion Cell ComplexA significant portion of retinal ganglion cells (RGCs) reside in the macula, a loss of tissue

in this region might be a sign of glaucomatous damageDefined as the three innermost retinal layers: the nerve fiber layer, the ganglion cell

layer, and the inner plexiform layer.Glaucoma likely preferentially affects these layers

Analyzing the GCC1. RTVue SDomain OCT--measures GCC thickness after centering a 7-mm2 area scan over

the fovea. The GCC is then automatically segmented by the software and displayed in three color-

coded maps for analysis.2. GCC analysis will become available in an expected software upgrade for the Cirrus HD-

OCT (Carl Zeiss Meditec, Inc., Dublin, CA). This software is under development and not yet commercially available.

FUTURE?In their study comparing GCC parameters with standard RNFL parameters, Tan and

colleagues also found that combining the two parameters significantly increased the detection rate of both preperimetric and perimetric glaucoma.

Newer software algorithms will likely combine RNFL, optic nerve head, and GCC

parameters to further increase the diagnostic yield of SD-OCT and will also lead to better reproducibility for accurate tracking of glaucomatous progression.

Pssst… Hey Doc between you and me…

86

87

88

89

90

91

92

93

94

95

96

97

98

1

9/24/2013

10

Marijuana and GlaucomaCannabis sativaSmall study of 11 patients, IOP was reduced 30% in 82% of the patientsDuration 3-4 hours ---(one drop of Xalatan up to 84 hours)local and systemic side effects associated with marijuana use. These include conjunctival

hyperemia, diminished tear production (leading to dry eye), pupillary mydriasis, alteration of blood pressure and cardiac arrhythmias

Marijuana and GlaucomaThe Bottom LineWhat can we tell patients who ask about marijuana use as a glaucoma treatment?

Perhaps the most precise answer is this: • Organizations such as the American Academy of Ophthalmology and the National Eye

Institute have determined that marijuana is not better or safer than other medical and surgical options available to manage glaucoma today.

• No studies have been published regarding the long-term ocular and systemic effects of marijuana use by glaucoma patients.

• The duration of action of smoked marijuana necessitates frequent use (four to six times daily), which is impractical.

• The psychogenic effects of regular marijuana use have been shown to hinder daily activity. –Review of Optometry, Sowka and Kabat 2007

Just Say?

Drug Eluting ContactsHarvard Medical Center ResearchersRecipients of MIT innovators in Life Sciences competitionDaniel Kohane, MD, PhD (anesthesiology)Coating Polylactic co-glycolic acid (PLGA) is coated with films containing Polyhydroxy-

methacrylate by UV polymerizationResearch is being funded by:

– National Institute of Medical Studies– National Eye Institute– Boston KPro foundation

Duration can be as long as 100 daysLimitation will be the duration of CL wear

Punctal Plugs with Latanoprost CoreQLT, Inc44-g Latanaprost Punctal Plug Delivery SystemPhase IIData:

– Mean change form baseline -3.5 mmHg– 36% showed reduction of >/= 5mmHg

99

100

101

102

9/24/2013

11

– Overall goal of 90% retention/ Initial 75%– Second generation plug 90%– Goal of therapy 90 days of Tx

Tracking the Elusive Diurnal!Sensimed: Swiss medical device company. Jean Marc Wismer CEODevice is called TriggerefishTracks fluid pressure in the eye and beams data to palm size recorder. Uses a circular antenna taped around the eye and connected to a battery powered

portable recorder.This transmits radio frequency energy to an utlra thin gold ring in the CL. This powers a

chip embedded in the lens.Additionally on the lens in an ultra thin platinum ring that stretches in response in

variation in eye shape secondary to pressure.Available in Europe. Primary trial at University Hospitals of Geneva

103

1

Glaucoma UpdateJ. James Thimons, O.D.,FAAOChairman, National Glaucoma SocietyDirector, Glaucoma Institute @ Ophthalmic Consultants

1. To Sleep Perchance to Dream!The Role of Sleep Dysfunction in Glaucoma

To Sleep Perchance to DreamSleep Dysfunction: It’s Role in patient HealthSleep Apnea: The Impact of sleep dysfunction in glaucoma

TO SLEEP PERCHANCE TO DREAMMOJON DS, etalOPTIC NEUROPATHY / SLEEP APNEAOPHTH 105:874-77 1998SEVEN PATIENTS3 SEVERE / NASAL STEPS 2 /ARCUATE DEFECT 32 MODERATE / ARCUATE DEFECT 1 MILDETIOLOGY- DECREASED BLOOD FLOW

Obstructive Sleep ApneaBendel, R et al.( Mayo Clinic, Jacksonville)OAS- Repeated apnea episodesDaytime symptomsDaytime sleepinessChronic fatigueDecreased cognitive function

EtiologyCollapse of the pharyngeal airwayLast 10-60 seconds

OSADiagnosisOvernight polysomnographyEEG, EMG, EOG EKG, Nasal buccal airflow,and pulse oximetry(arterial oxygen)

Respiratory Disturbance Index 10 >= OASS83 patients with apneaOutcomesMedian age 62Median RDI 37Median IOP 16mmHg

OSAOutcomes2.4% patients with OHTN33% COAG

1

2

3

4

5

6

7

2

No relation to gender , age, or BMIRelation between IOP increase and BMI level

Sleep Apnea & NTGMojon DS et al; Ophthalmologica 200216 patients with NTG had PSNRDI > defined as mild< 45 - 0%46-64 - 50%65 & > 63%

Sleep Apnea: The Silent AssassinCo-Morbidities of Sleep apnea Increased risk of CVAIrregular Menstrual Cycles (40%)Children May exhibit “ Failure to Thrive”: T & A removalPsychologic Dysfunction (32%)

2. Will The Real IOP Please Stand Up!

A Comparative Study of Tonometry in Controlled Glaucoma Patients

J James Thimons, O.D., FAAO

Tonometry on LASIK-treated Eyes

Pascal vs. GoldmannStudy Criteria:50 consecutive glaucoma patients45 full data base11 AA’s/ 5 L’sAge, sex, race, general healthMedications, Visual Fields (Sita 24-2 HVF), RNFL, C/D Ratio, Pachymetry & IOP’sAlternating Pascal vs. Goldmann Tonometry

Pascal vs: Goldmann15 (33%) Patients with Pascal IOP greater than 4 mmHg difference than Goldmann13 (28%) Patients with Pascal IOP greater than Goldmann2 (4%) Patients with Pascal IOP less than Goldmann

Pascal vs. GoldmannAverage age: 60.33Average Ta: OD 17.4/ OS 17.6Pachymetry: 537/539

8

9

10

11

12

13

14

15

16

17

18

3

RNFL: 71.22/ 75.38Medications: 1.22Visual Fields: 10.66/10.82C/D: 0.504 / 0.484

Pascal vs. GoldmannPascal IOP lower than GoldmannAverage IOP Ta: 30.6 / 34 mmHgAverage IOP Tp: 23.25 / 25.15 mmHgPachymetry: OD 623 / OS 625.5RNFL: OD 88.24 / OS 93.08C/D: 0.4/ 0.5VF loss: 3/2

Pascal vs: GoldmannPascal IOP greater than GoldmannGoldmann IOP: 16.3 OD/ 15.8 OSPascal IOP: 21.9 OD/ 20.6 OSRNFL: 66.56 / 69.32C/D: 0.7 / 0.72VF loss: 13.2 / 12.6Pachymetry: 516 / 518

Pascal vs: Goldmann5 patients (11%) with increased therapy2 patients ( 4%) with less therapy

Corneal Hysteresis:A New Ocular Parameter

3. Alternate Day Therapy in Glaucoma

Diurnal IOP Fluctuation & Visual Field LossGreater diurnal IOP fluctuation resulted in greater visual field progression

Home applanation tonometry by 64 patients 5X daily for 5 days Visual field progression of patients was tracked over 8 years

Asrani, et. al. Large diurnal fluctuations in intraocular pressure are anindependent risk factor in patients with glaucoma, J.Glaucoma, 9,134-142, 2000

Diurnal IOP Fluctuations and Glaucomatous Progression

Diurnal IOP Fluctuation in

19

20

21

22

23

24

25

26

27

28

4

Glaucoma Patients

Alternate Day TherapyTwice daily dosing increases IOP relative to once daily dosingXalatan and Lumigan combined can increase IOP, even to 50sanytime IOP is >30 with prostaglandin, it is overdosedOnce daily can be overdose if there is inflammation/endogenous prostaglandin

Persistence of IOP Response Labovitz RA et al; Arch Ophth 2001Comparison of Lumigan vs: TimololMaintenance of IOP at 48 hours post D/C 5.6mmHg 7.2 - 8.2 mmHg at peak effect28 Day control showed less thanTimolol was 3.4-3.9 mmHg at peak.

Alternate Day Therapy30% reduction first day, 25% reduction second day IOP will be one point higher on second dayGross. Journal of Glaucoma 2008Doro. ARVO 2007

Alternate Day TherapyReduced costReduced hyperemia, ache, dry eyeReduced long term conjunctival inflammation promoting trabeculectomy scarring

Alternate Day Therapy Post SLTSLT somewhat less effective in patients already on prostaglandinSuggesting that part of SLT induces prostaglandin like effects

QD prostaglandin could be an overdose after SLTEspecially first year after laser

Alternate Day Therapy: ComplianceNot a problem for organized patientsSome keep a calendarSome choose 3 or 4 days of the weekSome choose odd or even days

Alternate Day Therapy: Practical TipsStarting every other day improves tolerability in prostaglandin novicesAching and high IOP suggest overdoseWash face after instillation

Alternate Day Therapy: Initial Review22 patients with well controlled glaucoma over a two year period.Switched from daily therapy to alternate day treatment following complaints of cosmetic/

anterior segment problems

29

30

31

32

33

34

35

36

5

Average IOP pre-switch: 16.2 mmHgPost switch IOP at 1 week, 1month and 3 months average: 16.67 mmHg

4. Size Really Does Matter!

How to Evaluate Disc SizeUse a 60 D Lens at the Slit LampMake a Thin Vertical BeamMeasure Vertical Disc Diameter by Adjusting Beam HeightRead off Scale on Slit LampVertical Disc Diameter Greater Than 2.2 Mm Is a Large DiscVertical Disc Diameter Less Than 1.8 Mm Is a Small Disc

Optic disc size does not indicate glaucoma

Optic Disc Size

Optic Disc Size

Storing and Graphing Stereo Images and C/D Drawings.

TSNIT or ISNT Graphing

A Retrospective Study of HRT Data on 244 Referred Patients J. James Thimons, O.D.,FAAOMedical Director, OCCEric Conley, O.D.Assistant Professor, ICO

Average Age of HRT Scanned PatientsThe Average Age of the 244 Scanned Patients = 53.25 years oldThe Representative Age Range = 8 years to 93 years

Overall Review Optic Disc Area OD vs OS (mm2)Mean Disc Area OD = 2.17 (0.86 - 4.69)Mean Disc Area OS = 2.13 (0.81 - 4.60)

Data Analysis of Representative 244 HRT III Patients44 of 244 Patients Presented with Disc Areas >2.82mm2 (in at least on eye)

Data Analysis of Representative 44 Large Disc PatientsOnly 9 of 44 Patients with Macrodiscs Demonstrated Apparent Visual Field Loss80% of Patients Demonstrated No VF Loss

Data Analysis of Representative 44 Large Disc PatientsThe Overall Mean C/D Ratio of this Group = 0.55Average C/D OS = 0.65 (0.40 - 0.91)Average C/D OD = 0.61 (0.38 - 0.96)

5. Every Journey begins with The First Step

Staging Glaucoma & Target IOP

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

6

GON/Neuron Loss/HVF/OCT -RNFL/C/D1. 0-35% 0 to -2 < 80 0.1-0.7/52. 35-65% -2 to-5 <70 0.3-0.8/63. 65- 90% -5 to-15 < 60 0.6-0.9/7-84. > 90 % > - 15 < 50 0.8- 1.0 >9

Target Pressures Are Determined by the Baseline IOP and the Amount of Optic Nerve DamageMild Damage - 20-30% Reduction of Baseline IOPModerate Damage - 30-40% Reduction of Baseline IOPSevere Damage - 40-50% Reduction of Baseline IOP

Visual Field Classification (Mild, Moderate, Severe)Mean Deviation (MD)Number of Abnormal Points on the Pattern Deviation PlotsDecibel Value of the Four Points Just Off Fixation

Mild Visual Field DefectThe Mean Deviation Index (MD) Is Better Than -6 dBOn the Pattern Deviation Plot, Fewer Than 18 of the Points Are Depressed Below the 5%

Level and Fewer Than 10 Points Are Depressed Below the 1% LevelNo Point in the Central 5 Degrees Has a Sensitivity < 20 dB

Moderate Visual Field DefectThe Mean Deviation Is Better Than -12 dBOn the Pattern Deviation Plot, Fewer Than 36 of the Points Are Depressed Below the 5%

Level and Fewer Than 20 Points Are Depressed Below the 1% LevelNo Point in the Central 5 Degrees Has a Sensitivity < 10 dB

Severe Visual Field DefectThe Mean Deviation Is Worse Than -12 dBOn the Pattern Deviation Plot, More Than 36 of the Points Are Depressed Below the 5%

Level or More Than 20 Points Are Depressed Below the 1% LevelAny Point in the Central 5 Degrees Has a Sensitivity <10 dBThere Are Points Within the Central 5 Degrees With Sensitivity <20 dB in Both Hemifields

6. The Role of Perfusion Pressure in Glaucoma

Hypoperfusion•• flow = pressure/resistance• perfusion pressure = BP - IOP• mean arterial BP = diastolic + 1/3 syst-diastolic• nocturnal hypotension is greatest risk

Nocturnal Hypotension: Another Reason to Get a Good Nights SleepTIBA MedicalABPM 240024 hour Serial BP MonitoringRole in Glaucoma Management

Nocturnal Hypotension

52

53

54

55

56

57

58

59

60

7

TIBA MedicalReimbursementCommercialMedicare

ICD-9 Codeswww.tibamedical.com

How Low Can You Go! SM a 40 y/o white female was referred for evaluation of glaucoma. Current Tx was

Betoptic-S and Alphagan.VA 20/20 OD/OSTa 12/12 @ 10SLE: wnlDFE: 0.7 OD / 0.9 OSVF: Early near fixation loss OSGonioscopy: CB 360 OUMedical Hx: LBP ( 100/65), pulse 54, Raynaud’s, Migraine HAFamily Hx: Negative

Visual Field Loss

How Low Can You Go!4/21/07Meds: Alphagan P, Lumigan, GinkgoTa:14/11 @ 9:30Migraines increased x 4 weeks, episode of syncope x 1 weekSerial BP 2 AM 58/30/ pulse 54

NTG- Differential DiagnosisDiurnal VariationVasculitisOptic AtrophyOld AIONPrevious RBON

Compressive ONChronic marijuana usePrior Hypotensive episodesSystemic Beta-Blocker “Burned out” GlaucomaSub-acute angle closure

61

62

63

64

65

66

67

68

1

2

8

History steroid useOcular Ischemic Syndrome

Nocturnal Hypotension: It’s role in Visual Field ProgressionGraham SL, Drance S: Surv Ophthalmol Jun 199984 patients 24 hour ambulatory BPNocturnal BP variables were lower in patients with progressive VF lossPatients with > nocturnal dips were more likely to show VF loss even with good IOP

control Increased risk of disc hem’s

NORMAL TENSION: ABNORMAL RESULTSANDERSON et al AJOEXAMINED NTG’S FOR MULTIPLE VARIABLES (AGE, GENDER,BP AND MIGRAINES)MIGRAINES,DISC HEM’S MOST NOTABLE RISK FOR PROGRESSIONAGE , RACE NEXT230 PATIENTS/NTG/IOP< 20mm Hg

NTG99 WOMEN/61 MEN23 WOMEN WITH H/O MIGRAINES2 MEN WOMEN WITH MIGRAINES HAD FASTEST RATE OF PROGRESSION

THE BIG DIPPERSTIMADA K etal, CIRCULATION 1990 COLLIGNON N etal INT OPH 1998NOCTURNAL HYPOTENSION OCURS IN 10% OF POPULATION“BIG DIPPERS” > 10%INCREASED RISK OF MI AND LOWER LIMB ISCHEMIAINCREASED RISK OF VF LOSS AND DISC DAMAGE

Nocturnal and Diurnal Habitual IOP

Treatment of Low Blood Flow• middle aged women with history of low BP

• increase salt• licorice extract (glycerrhinic acid) is aldosterone agonist

• elderly patients taking BP meds with BP <130/75• if no heart disease or stroke, discuss reduced anti-hypertensive therapy

7. SLT: 1st, 2nd & 3rd Line Therapy

Selective Laser Trabeculoplasty (SLT)

Laser trabeculoplasty

Stimulates trabecular cells to release mediators which improve outflowImproves both trabecular and uveoscleral outflowUseful in all open angle glaucoma except uveitic and neovascularEffectiveness and response rate similar to Xalatan (25% reduction in 80% of patients

69

70

71

72

73

74

75

76

77

9

not receiving other treatment

Selective Laser TrabeculoplastyResults comparable to ALT (argon laser trab.)50 spots to nasal trabecular meshwork Less “traumatic” than ALT70% of pts respond IOP reduced by > 3 mmHg, mean 23.5%

SLT Effectivity• International studies show IOP reductions of 22%-28% with 36-49 weeks follow-up In a prospective, randomized clinical trial, SLT and ALT were shown to have a similar

effect on IOP reduction

Laser Trabeculoplasty risks20% of patients get minimal benefit IOP spikeLess likely if treatment is fractionated into 2-4 sessions per eyeGreater risk in pigment dispersion

Making Sense of Normal Pressure GlaucomaAsrani, S et al; ARVO 200624 eyes of 12 untreated patients Analyzed IOP fluctuation before and after SLTOutcomes:Mean IOP decrease was 1.89 OS & 2.06 ODMean Diurnal pre SLT: 5-10 mmHgMean Decrease in Diurnal IOP 2.78 OS/ 5.73 OD

Greater decrease in Diurnal than Mean IOP

8. Trab’s vs Tubes: A New Paradigm

TUBE SHUNT SURGERYTube in anterior chamber connects to a reservoir sutured to posterior globereservoir (plate) prevents scar from blocking tube openingscar around reservoir will limit IOP

Common tube typesAhmed has a valve to limit early hypotonyBaerveldt has larger surface area1-2 points lower than Ahmedbut greater risk of suprachoroidal hemorrhage

TUBE PROBLEMSGradual failure due to scarring around reservoirErosion of tube through conjunctiva

78

79

80

81

82

83

84

85

86

87

10

Consequent serious risk of infectionDecompensation of corneal endotheliumcan occur even without contact of tube and endotheliumcorneal transplants usually fail over several years if tube is in anterior chamber tube can be moved to posterior chamber after vitrectomy

Physiologic outflow Two subsections:Trabecular meshworkSchlemm’s canal and episcleral veins

Conventional fistulization surgery bypasses bothNon-penetrating may bypass just TM or both sections

9. OCT & it’s Use to Stage Glaucomatous Optic Neuropathy &

Nerve Fiber Layer Analysis• OCT overestimates RNFL thickness in large discs• Underestimates RNFL in Hypoplastic disc’s• average thickness is best gauge of overall damage• Sectoral damage must match ONH topography• 70 microns is moderate loss, 60 advanced, 50 severe

10. Canaloplasty: Surgery for the 21st Century

Glaucoma: Not Just a Goal pressure Lee AJ et al; Ophthalmology 2006COAG & CAD Mortality: The Blue Mountain Study3,654 patients 49-97 evaluated over 9 yearsAll cause mortality 24.3% non COAG / 23.8% COAGCardiovascular Mortality 8.4% non COAG/ 14.6% COAGObserved mainly in < 75 y/o with previously diagnosed disease

Glaucoma: Not Just a Goal PressureSuh-Yuh Wu et al; Arch Ophth 2008Open angle Glaucoma & Mortality: The Barbados Eye Studies4092 AC’s/ 40-84 / 9 year evaluation764 deaths/ unrelated to overall mortalityCardiovascular mortality increased with previously diagnosed disease ( 1.38) and timolol

maleate use ( 1.91)

Glaucoma: Not just a Goal PressureBroman, TB, Quigley H, et al Investigative Ophth 2002 Impact of Visual Impairment and Eye Disease on Visual-Related Quality of Life4774 participants/ NEI-VFQ 25

88

89

90

91

92

93

94

95

96

97

98

11

Glaucoma patients scored lower without decreased visual acuity than matched groups

IOP in glaucomaA risk factor Poor for diagnosing POAGPoor predictor of disc and field damageUsed for management (AGIS - target IOP) Normal population distribution skewed (non-bell shaped) Overlap between normal and glaucoma groups

ANOTHER REASON NOT TO BE A COUCH POTATOE !PASSO, M etal; Arch Ophth-Vol 109 Aug 1991EXERCISE TRAINING REDUCES IOP AMOUNG GLAUCOMA SUSPECTS13 SEDENTARY ADULTS/25-60 Y/O< 1 HOUR/WEEK OF EXERCISE PRIOR TO STUDY FOR 6 MONTHSIOP > 22mmHg MULTIPLE MEASUREMENTS

EXERCISE AND IOPBASELINE COMPREHENSIVE EXAM12 WEEKS/ 40 MINUTES /DAY/4 DAYSOUTCOMESBASELINE IOP 23.8 mmHgPOST TRAINING IOP 19.2 mmHg

SYSTEMIC RESPONSE SIMILAR( BP, HEART RATE ) IOP AFTER DECONDITIONING 24mmHg

99

100

101

9/24/2013

1

Advances in Medical & Surgical Anterior Segment TherapyJ. James Thimons, O.D.,FAAOOptometric Medical DirectorOphthalmic Consultants of Connecticut

Cross Linking: New Technology for and Old Disease

KCN DiagnosisCorneal HydropsMunson’s signApical ScarringVogt’s StriaeIrregular MiresAbn(anterior)Topo High ComaEpithelial thickness abnormalitiesPosterior Corneal CurvatureRelative pachymetry

Corneal Collagen Cross-LinkingCreates chemical bonds between fibers

Floppy Eyelid Syndrome

Classic PatientMale age 30-70Overweight or obeseChronic irritation, tearing, redness, dischargeProblem worse on the side on which he sleeps

Cross-Linking is Not NewHardening of polymers in materials science since 1930s (silicone oil→rubber ball)Dentists X-linked for decadesNormal aging of connective tissue involves cross-linking and stiffeningProgression of KCN↓ with age as XL↑

We All “Crosslink” as we Grow Up

Transplant Risks

Managing Graft FailureTopical TherapyOral Antibiotic TherapyOral Steroids

1

2

3

4

5

6

7

8

9

10

11

9/24/2013

2

Bacterial Flora of the Normal Eye/AdultsStaphylococcus epidermidis 75-90%*Diphteroids (C. xerosis) 20-33%Staphylococcus Aureus 20-25%*Streptococcus (S. viridan) 2-6%Hemophilus influenza 3% or moreStreptococcus pneumoniae 1-3%*Gram negative rods 1% or more*Pseudomonas aeruginosa 0-5%*

* Dominant organisms in microbial keratitis

Body depots of bacterial organismsSkin: Lids/hands: Staph/Gr. (+)Nose/nasopharynx: Staph and GR (+)Kids: HemophilusOropharynx: Staph and StrepGr (+)Mouth: Strep/BacteroidesStomach: Helicobacter pylori and rosaceaeSmall Intestine: Gr (+) cocci and bacilliLarge intestine: Greatest conc of bacteria in body (10 organisms/gm) anerobes-

enterobacteria, enterococcus feacalis, E. coliGenito-urinary tract: Chlamydia, E. coli, Neisseria gonorrhea (Ophthalmia neonatorum)

Bacterial conjunctivitisIn adults, 75% of cases caused by Gram positive pathogens

– Staphylococcus epidermidis, S. aureus, Streptococcus pneumoniaeVery common in children under 6 yearsCausal agents of pediatric cases:

– 42% Haemophilus influenzae– 35% S. pneumoniae

Common Ocular PathogensGram (+)Staph epidermidisCoagulase negativeOpportunistic pathogenFrequent cause of CL keratitisNormal floraChronic bleparitisStaph aureusCoagulase positiveMethacillin resistant strainExotoxinsInflammatory diseaseAbscess formationSevere keratitis

12

13

14

15

9/24/2013

3

Strep Species (GR+)Strep pneumonaeEnzymes/virulenceSeen in cold climatesPerforate in 7 daysassociated with erysipilus cellulitis

Gram (-) speciesPseudomonasHemophilusKlebsiellaSerratiaMoraxellaNeiserria

Important PenicillinsAmpicillin: Broad spectrum oral-QID dosingAmoxicillin: Pro-drug of Ampicillin, improved absorption with lower GI side-effectsCloxacillin/Dicloxacillin: Intrinsic beta-lactamase resistanceAugmentin: Amox + ClavulanateMethicillin: IV prep for penicillinase producersAmp + Sulbactam: Unasyn: IV

Ticarcillin + Clavulonic acid: IV better penicillinase protection than methacillin

AugmentinIndications/Dosage formsIndications:Preseptal cellulitisDacryocystitisPediatric Hemophilus Amoxicillin + Clavulanate@@@@Dosage forms:500 or 875mg tablets BID125 or 250mg/5cc pediatric suspension

Before and After Crosslinking

CXL in KeratoconusShown safe and effective worldwideArrest progress of KCNImprovement in UCV, BCSVA, CLsIdeal candidates ≤ 45 y/o, corneal thickness ≥ 400 µm, limited scarringMinimum age in Europe now 10 y/o

CXL and EctasiaKannalopoulos, JReview of CXL post LASIK with ectasiaAnalysis at one year

16

17

18

19

20

21

22

9/24/2013

4

– Corneas stable– Mild refractive error shift

No PK required at two years

CXL and PRKRequires wavefront scan at level 4 reliabilityPredictability is less than standard PRKContraindicated with apical scarPost-op similar to standard PRKCL’s same algorithm

Radial Keratotomy

CXL TechniqueAnesthetic drops, painlessPrepare corneaRiboflavin drops for 30 minsUV light for 5 or 30 minutes dependent on energy source Bandage contact lens

UV-A Light 370

CXLPost-operative Care

– 1 day, 1 week, & 1 month recommended visits– 4th generation fluoroquinolone qid– Durezol qid– BCL– NPATS

Haze?

CXLPost CXL Contact Lens Management

– 3 weeks soft lens– 4 weeks Hard CL or “Piggyback”– 6 weeks for Complex Lens fit

Topo’s at 3M/ 6MCrosslinking can continue up to 6M

Case 2: 22M KeratoconusNo glasses, can’t tolerate hard CL OSUCVA:

OD 20/15OS 20/100

Manifest Rx: OD +1.00-1.25x85 (20/15)

23

24

25

26

27

28

29

30

31

32

9/24/2013

5

OS -0.25-2.50x159 (20/40)Keratometry:

OD 42.25 x 43.00OS 43.50 x 47.00

Case 2: Topography

Case 2: Pentacam OD

Case 2: Pentacam OS

Case 2: 22M KCN, no complaintsOPTIONS for “normal” OD1)Observation2)RGPCL3)CXL alone4)Intacs + CXL

Step 1: Intralase Intacs Channel Creation

Step 3: CrosslinkingRiboflavin drops every 2 min x 30 minPachymetry checked > 400 umCheck UV light source calibrationUV light source applied focused onto the corneaRiboflavin drops instilled every 2 min while UV light application for 5/30 min1 drop of fluoroquinolone and steroid Bandage contact lens

Post-Operative Management IssuesInfection Symptoms

• Pain - Hallmark• Photophobia• Decreased Vision

Findings• Infiltrate

at Incision or in Tunnel

Medication

Indications for IntacsContact lens intoleranceTo delay corneal transplantModerate KCN (K > 55D)

33

34

35

36

37

38

1

39

40

41

42

43

9/24/2013

6

Post-LASIK ectasiaClear central corneaPachymetry at least 450 um at incision

LipiFlow / LipiViewA New Paradigm in Meibomian Gland Disease Treatment

Traditional MGD TherapyThe CyclinesOM3’s

The CyclinesTetracycline, Doxycycline and Minocycline

– Isolated from Streptomyces– Effective against Gram +/ Gram -/Aerobic/ Anerobic/ Spirochetes/Rickettsia/Chlamydia– Similar action / different duration

The CyclinesClinical Applications

– Brucellosis– Rickettsia ( Rocky Mountain Spotted fever)– Lyme Disease– Chlamydia/ Trachoma– Primary Meibomianitis– Gonococcal Prophylaxis– “Corneal melting” Syndrome– Non Healing Corneal lesions– Rosacea–

TearScience® Solution

MGD and Lipid Layer Thickness“ConclusionsLipid layer thickness objectively measured with the interferometer was significantly thicker in the control group than in the obstructive MGD group. Lipid layer thickness was negatively correlated with upper and lower meibomian gland losses in the control group as well as in the obstructive MGD group.”

Youngsub Eom, Jong-Suk Lee, Su-Yeon Kang, Hyo Myung Kim, Jong-Suk SongDepartment of Ophthalmology, Korea University College of Medicine, Seoul, South KoreaFebruary, 2013

Correlation Between Quantitative Measurements of Tear Film Lipid Layer Thickness and Meibomian Gland Loss in Patients With Obstructive Meibomian Gland Dysfunction and Normal Controls

LipiView® Output

44

45

46

47

48

49

50

51

9/24/2013

7

Produces a measurement called the Ocular Index of Lipid Interferometric Color Unit (ICU)Calculated on a frame-by-frame basis and plotted for ~1 billion data points per eyeThe results are then displayed and are available for printout

Meibomian Gland Expression and Gland Functionality“There are multiple reasons why obstructive MGD may not be detected. If there are no obvious eyelid or meibomian gland orifice changes, obstruction would not be expected and could not be detected without diagnostic expression… It is only if the meibomian gland orifices evidence changes such as pouting, protruding plugs, recession, or surrounding inflammation that MGD and/or meibomian gland obstruction would normally be suspected. Expression of the gland is therefore vital for diagnosis…”

Blackie, et alNonobvious Obstructive Meibomian Gland Dysfunction

Cornea 2010

Because Not All MGD Is Obvious, Active Disease Identification Is Crucial

Normal Meibomian Glands

Meibomian Glands

LipiFlow® Thermal Pulsation System

LipiFlow® Thermal Pulsation System

LipiFlow® Offers a Solution for Patients With MGD

Therapeutic Goal of Pulsation

LipiView/ LipiFlowLipiView

– Reimbursement: $ 125.00Lipiflow

– Reimbursement: $1000.00-1,500.00

Point of Care Diagnostic Systems: The Next Step in Anterior Segment CareRPS AdenodetectorTear LabLacriPenInflammaDry

Laboratory Testing Primary Care: A Paradigm ShiftEvery specialty other than Eye Care Practitioners (ECP) couldn’t practice without Lab

52

53

54

55

56

57

58

59

60

61

62

63

64

9/24/2013

8

Tests– Cholesterol – Strep throat

FACT: Impacts 70% of all medical decisions / represents less than 3% of healthcare costs

Only ECP do not have luxury of using reference laboratories– Must become a CLIA tear testing laboratory

Primary Outcome - Clinical– Better patient care / satisfaction– Can “manage” the Disease (i.e. Disease Management)– Accredited Dry Eye Center (ADEC)

Laboratory TestingDifferent from Procedure test!!!Lab tests are to rule-in or rule-out.Procedures are to document the disease that has been seenOnly 3% of the total medical expense for patient care is for labsYou as the clinician determine what is indicated based on Hx, symptoms &/or signs• Patients with a History of DED or Symptoms: e.g. Fluctuating Vision, Contact Lens Discomfort, Light Sensitivity, Watery

Eyes, Tired Eyes, Redness, Burning, Itching, Sand or Grit, Cataract, Glaucoma, Diabetes, or

Signs: lid abnormality, corneal/conjunctival abnormality

Acute Conjunctivitis Affects approximately 2% of the population annually 1-2% of all office visits 20-70% is viral conjunctivitis 65-90% is caused by Adenovirus Adenovirus is associated with significant morbidity and high healthcare costs

Adenoviral Conjunctivitis Represents the most common external ocular infection1

Most frequent virus isolated from the conjunctiva2

Prevalence varies based on time of year and geographic location3

20-65% of all conjunctivitis cases are viral2

−As many as 90% of these may be Adenovirus3

Clinical Accuracy No evidence exists to support the diagnostic usefulness of clinical signs, symptoms, or

both in distinguishing bacterial conjunctivitis from viral conjunctivitis Leibowitz et al. – Only 31% of presumed bacterial conjunctivitis were culture positive

whereas 52% with presumed viral conjunctivitis were culture positive for pathogenic bacteria Cheung et al. – 67% of Adenoviral cases presented unilaterally

65

66

67

68

9/24/2013

9

and the misdiagnosis rate was 42% in these patients During a clinical trial to evaluate cidofovir treatment at 16 academic centers, experts

showed a clinical accuracy of about 48%

Competitive Advantages: RPS vs Traditional Testing

AdenoPlus Detects all known serotypes of Adenovirus Rapid – 10 minute results Easy to use – can be performed by a nurse or technician In-office (point-of-care) test Low cost – no additional equipment required One time use – disposable Accurate – high sensitivity and specificity Limit of detection – 6 ng/ml

RPS Adeno Detector Plus

How to Use AdenoPlus: Four-step Process

InflammaDry

InflammaDry: Defining the Role of MMP-9 in Dry Eye? Matrix metalloproteinases (MMP) are proteolytic enzymes that are produced by stressed

epithelial cells on the ocular surface 1

Non-specific inflammatory marker Normal range between 3-41 ng/ml More sensitive diagnostic marker than clinical signs 1

Correlates with clinical exam findings 1

Ocular surface disease (i.e. Dry Eye) demonstrates elevated levels of MMP-9 in tears 1

MMP-9 and Dry Eye Severity1

Limit of DetectionThe normal level of MMP-9 in human tears ranges from 3-41 ng/ml

Positive test result = MMP-9 ≥ 40 ng/mlNegative test result = MMP-9 <40 ng/ml

69

70

71

72

73

74

75

76

77

78

79

9/24/2013

10

How to Use InflammaDry: Four-step Process

Future Advances in Tear Marker AssessmentTear markers that currently exist:IgE, HSVAlzheimer'sDiabetesParkinsons?

375.15 Tear Film Insufficiency, Unspecified; Dry Eye Syndrome370.33 Keratoconjunctivitis sicca, not specified as Sjögren's syndrome710.2 Sicca syndrome, keratoconjunctivitis sicca Sjögren's disease365.11 Primary open angle glaucoma373.12 Meibomian gland infection373.71 Hyperemic conjunctiva370.23 Filamentary keratitis371.42 Recurrent corneal erosion375.21 Epiphora excess lacrimation375.22 Epiphora insufficient drainage374.01 Entropion 374.10 Ectropion375.51 Punctal eversion375.52 Punctal stenosis375.41 Canaliculitis372.21 Angular blepharoconjunctivitis372.22 Contact blepharoconjunctivitis373.01 Ulcerative blepharitisICD-9 Diagnostic Codes

Tear Function Screening QuestionnaireGritty or sandy sensation?Pain or soreness?Fluctuating vision?Occasional Tearing?Blurred vision while reading?Discomfort in windy conditions?Discomfort in air conditioned areas?Itching?

Possible Testing During Dry Eye Evaluation

80

81

82

83

84

1

2

85

86

87

9/24/2013

11

Tear Break Up Time

Conjunctival StainingModerate / Severe lissamine green staining

Schirmer Strips

Summary Statistics on Tear OsmolarityNormal subject average:

– 296 ± 8 mOsm/LDry Eye subject average:

– 323 ± 16 mOsm/LNormal subject inter-eye difference:

– 7 ± 6 mOsm/LDry Eye subject inter-eye difference:

– 17 ± 15 mOsm/L– Inter-eye difference is the hallmark of DED ( > 8 mOsm/L between eyes)1

Osmolarity in the Diagnosis of Dry Eye DiseaseOsmolarity is the “gold standard” test for Dry Eye

– 45 years peer reviewed research– Osmolarity has been added to definition of Dry Eye– Global marker of Dry Eye, indicating a concentrated tear film

Tear Osmolarity (Tomlinson 2006)

KEEP IT SIMPLE AND TAKE ADVANTAGE OF PPVMILD RANGE:

– 300-320 mOsmol/L–

MODERATE RANGE:– 320-340–

SEVERE RANGE:– > 340–

–

Osmolarity & Tear Film Instability in DED

Two Numbers Crucial to Understand Osmolarity The MAXIMUM of the two eyes: 314Tears higher than 300 mOsm/L demonstrate loss of homeostasis and likely become pathogenetic > 308

88

89

90

91

92

93

94

95

96

97

98

99

1

9/24/2013

12

The DIFFERENCE b/w two eyes: 24This tells you how stable the tear film is. Normal tears are stable and < 300 mOsm/L bilaterally. A difference of > 8 mOsm/L is a hallmark of tear instability.

Tear LabReimbursement

– NGS:$ 44.50– Medicaid: $ 43.50– Commercials: $ 29-40

Code: 92071Card cost: $10

Symptoms of Dry Eye

Signs of Dry Eye

Potential Chronic ChangesTelangiectasiaDislocation of meibomian glands/ gland atrophy

Scarring

Treatment Recommendationsby Severity LevelsLevel 1

– Education and environmental/dietary modifications– Elimination of offending systemic medications– Artificial tear substitutes, gels/ointments– Eye lid therapy

The Hypothesis behind“The Root Cause” of Dry EyeOmega Imbalance (excess Omega-6:Omega-3)

– causes the meibum to become thick, viscous and inflamed – causes the Meibomian Glands to become blocked – prevents the production of the lipid layer

Without the lipid layer, the aqueous layer evaporates, causing the ocular surface to become irritated (red, dry, scratchy)

Dosing Protocol – Dry Eye Omega Benefit Therapeutic Dose -Four capsules daily with meals

Treatment Recommendationsby Severity LevelsLevel 2:

– If Level 1 treatments are inadequate, add:Anti-inflammatory agentsTetracyclines (for meibomianitis, rosacea)

2

100

101

102

103

104

105

106

107

108

9/24/2013

13

Punctal plugsSecretagoguesMoisture chamber spectacles

EXTEND™ Synthetic Absorbable Implant

Billing for Punctal Occlusion68761 Punctal Occlusion Permanent or Temporary

– E CodesE1 Superior LeftE2 Inferior LeftE3 Superior RightE4 Inferior Right

– NGS reimbursement: $168.64– Silicon Plug cost: $40-50– Extended Collagen: $7-8––

Developing Treatment ProtocolsNutritional Supplements

– Omega 3 fatty acidFish Oil (EPA and DHA)Flaxseed

– GLA– Vitamins

Treatment Recommendationsby Severity LevelsLevel 3:

– If Level 2 treatments are inadequate, addSerumContact lensesPermanent punctal occlusion

Treatment Recommendationsby Severity LevelsLevel 3:

– If Level 2 treatments are inadequate, addSerumContact lensesPermanent punctal occlusion

109

110

111

112

113

114

115

116

9/24/2013

14

Moderate to SevereAutologous Serum:

– Blood draw 30 cc (~$15)– Spin @ 4000 RPM for 20 min.– Serum placed in container– Makes 6-7 containers 5 ml (mix with sterile water) 3mo supply– Some put antibiotic in e.g. – Freeze all containers except one being use– Dose q2h beginning then adjust – Cost of compounding pharmacist ~$120 –

Treatment Recommendationsby Severity LevelsLevel 4:

– If Level 3 treatments are inadequate, addSystemic anti-inflammatory agentsSurgery (lid surgery, tarsorrhaphy; mucus membrane, salivary gland, ammiotic membrane transplantation)

Persistent Epithelial DefectsTreatment

cyanoacrylate tarsorrhaphy–Indicationslagophthalmosexposure keratitisneurotrophic keratitisdry eyespersistent epithelial defects

Persistent Epithelial DefectsTreatment

cyanoacrylate tarsorrhaphy–Indicationslagophthalmosexposure keratitisneurotrophic keratitisdry eyespersistent epithelial defects

Temporary Cyanoacrylate TarsorrhaphiesAge (27-85) 62Dx:

– Persistent epithelial defects (12)– Neurotrophic keratitis (02)– Exposure keratitis (02)– Lagophthalmos (01)

117

118

119

120

121

9/24/2013

15

ProKera HSK TherapyOral anti-viralsTopical Anti-virals?

Famvir (famciclovir)Pharmacology:

–Synthetic nucleoside (guanine) analog, prodrug of penciclovir. Penciclovir conversion into acyclovir triphosphate inhibits herpes virus-specific polymerases & produces viral DNA termination.

Formulation: –125, 250 and 500 mg tablets.

Usual Dosage:–Adults: 500 mg q8h x 7 days (HZV)–Children: Safety not fully evaluated.

Indications: –HZV ophthalmicus, suppression of recurrent HSV keratitis.Safety/efficacy of long-term HSV suppressive txnot fully established.

Valtrex (valacyclovir HCl)Pharmacology:

–Synthetic purine (guanosine) nucleoside analog, prodrug of acyclovir. Valacyclovir is almost completely converted toacyclovir by first pass intestinal and/or hepaticmetabolism.

Formulation: –500 and 1000 mg tablets.

Usual Dosage:–Adults: 1000 mg q8h x 7 days (HZV).–Children: Safety not fully evaluated.

Indications: –HZV ophthalmicus, suppression of recurrent HSV keratitis.Safety/efficacy of long-term HSV suppressive tx not fully established, but likely comparable to acyclovir.

122

123

124

125

126

127

128

129

9/24/2013

16

Zovirax (acyclovir)Pharmacology:

–Synthetic purine (guanosine) nucleoside analog. Acyclovir is phosphorylated by the enzyme thymidine

kinase which is encoded by herpes viruses (HSV-1, HSV-2, HZV). Acylovir triphosphate selectively

inhibits herpes-specific polymerase which, in turn, produces viral DNA termination.

Formulation: –400 and 800 mg tablets.

Usual Dosage:–Adults: 800 mg 5x qd x 7 days (acute HZV).–Children: Safety and efficacy not fully evaluted in ocular disease mgmt.

Indications: –HZV ophthalmicus, suppression of recurrent HSV keratitis.400 mg bid for up to 1 yr. for chronic suppressive tx. (greatest benefit in recurrent, vision threatening stromal HSV keratitis or cases where vision loss from HSV epith. keratitis is a concern).

ProKeraReimbursement

– $1,628.38Code: 65778

Oculoplastic Procedures for the Primary Care ClinicianJ. James Thimons, O.D., FAAO

Comprehensive Lacrimology TherapyIncludes Therapeutics

– Topical– Oral

Includes Punctal OcclusionDilation & IrrigationNasolacrimal Probed Multiple Medical Visits

Predisposing factorsAgeGenderEnvironmentAnterior Segment DiseaseMedicationsCL Wear

130

131

132

133

134

135

136

137

1

2

9/24/2013

17

Refractive surgerySystemic Disease

Pathophysiology of Epiphora Increased Reflex Tear Production

– Rapid tear break up time– OSDI– Ocular surface irritation– Corneal changes:Punctate epithelial erosionsInfiltrates related to staph hypersensitivity

Decreased Outflow– Punctal Stenosis– Naso-Lacrimal obstruction– Anatomic AbnormalityFloppy LidEctropian/EntropianTrichiasis

– Dacryocystitis

Managing DacryocystitisAntibiotic Therapy

Important PenicillinsAmpicillin: Broad spectrum oral-QID dosingAmoxicillin: Pro-drug of Ampicillin, improved absorption with lower GI side-effectsCloxacillin/Dicloxacillin: Intrinsic beta-lactamase resistanceAugmentin: Amox + ClavulanateMethicillin: IV prep for penicillinase producersAmp + Sulbactam: Unasyn: IV

Ticarcillin + Clavulonic acid: IV better penicillinase protection than methacillin

AugmentinIndications/Dosage formsIndications:Preseptal cellulitisDacryocystitisPediatric Hemophilus Amoxicillin + Clavulanate@@@@Dosage forms:500 or 875mg tablets BID125 or 250mg/5cc pediatric suspension

Plan B: The cephalosporinsMechanism: Same as penicillinBacteriostaticLow toxicity

138

139

140

141

142

9/24/2013

18

3% allergic to pen are allergic to Ceph.Better penicillinase resistance than penicillins

Second Generation: Greater Gram (-) activity,especially HemophilusCefaclor: PO-CeclorCefuroxime: PO-Ceftin

Third Generation: Reduced GR (+) activity (Staph sp) with marked Gr (-) activityCefixime: PO- (Suprax)Cefpodoxime: PO - VantinCefprozil: PO - Cefzil

Anatomy

Illustrative Problematic Case60 yo white female with long standing history of blepharitis associated with acne rosaceaHas been on various blepharitis regimens and seen numerous eye care providers Continues to have daily, intermittent pooling of tears and carries tissue to wipe her eyesExam shows improved appearance of her lid margins

Cicatricial EctropionChronic irritation from blepharitis and tearing can lead to cicatricial changes of eyelid skinChronic wiping can exacerbate age-related laxity of lidExposure and hypertrophy of conjunctiva increases tendency of lid to evert

Floppy Lid SydromeC:\Documents and Settings\James Thimons\Desktop\photo.JPG

Punctal Stenosis

Dilation & IrrigationEquipment

– Sterile saline– Pediatric/Adult dilator– 1 or 3 ml syringe– 135 degree canulla

Clinical pearl: Use antibiotic or steroid in syringe to enhance taste by patient

Naso-lacrimal ProbeEquipment

– Pediatric / Adult dilator

143

144

145

146

147

148

149

150

151

152

153

154

9/24/2013

19

– Bowman’s probe( multiple diameters)– Sterile saline– Anesthetic– Syringe– Cannula

..\Desktop\photo.JPG

..\Desktop\photo.JPG

..\Desktop\photo.JPG

Mini MonokaFCI ophthalmics

Punctal/Canalicular Intubation for Punctal Stenosis Advantages

– Quick, in office procedure under topical anesthesia– In experienced hands, essentially no risk– Easy to remove

Disadvantages– Epiphora may increase over short term due to footplate occlusion of punctum– Problem may recur if underlying inflammation inadequately treated– No good billing code for procedure–

Self retaining bicanalicular intubationFCI ophthalmics

Naso-Lacrimal ProceduresRe-imbursement

– D&I: $143.15– NLP: $278.61

CodesD&I 68801NLP 68810

Anterior Segment Surgical ProceduresDebridementAnterior Basement Membrane MicropunctureComplex Foreign Body Management Cyanoacrylate Procedures

155

156

157

158

159

160

161

162

163

164

165

9/24/2013

20

Recurrent ErosionsPathophysiology - basal epithelial basement membrane misdirection results in:

– Thickened basement membrane– Reduplicated basement membrane– Intraepithelial pseudocysts– Lack of hemidesmosomes

Recurrent ErosionsClinical Etiology

– PrimaryEpithelial dystrophies (MDF, Meessman’s)Bowman’s membrane dystrophy (Reis-Bucklers)Stromal dystrophies (macular, lattice, granular)

Rodriguez MM, Fine BS, Laibson PR, Zimmerman LE. Disorders of the corneal epithelium. A clinicopathologic study of dot, geographic, and fingerprint patterns. Arch Ophthalmology 1974;92:475-82

Recurrent ErosionsContributing Factors

– Dry eyes– Blepharitis– External disease / tear film abnormalities

The CyclinesTetracycline, Doxycycline and Minocycline

– Isolated from Streptomyces– Effective against Gram +/ Gram -/Aerobic/ Anerobic/ Spirochetes/Rickettsia/Chlamydia– Similar action / different duration

The CyclinesClinical Applications

– Brucellosis– Rickettsia ( Rocky Mountain Spotted fever)– Lyme Disease– Chlamydia/ Trachoma– Primary Meibomianitis– Gonococcal Prophylaxis– “Corneal melting” Syndrome

166

167

168

169

170

171

172

173

174

175

176

177

9/24/2013

21

– Non Healing Corneal lesions– Rosacea–

Recurrent ErosionsSurgical Management

– Epithelial debridementchalazion curette57 Beaver Blade

Case A 46 y/o male physician 5 years s/p LASIK complains of decreased vision OD over past 4

years presents for refractive consultation for CXL.– ManifestOD +1.25-4.25 X 95 20/70

– PachymetryOD 460 microns

file:///C:/Documents%20and%20Settings/James%20Thimons/Desktop/Debridement%20video.htm

Recurrent ErosionsAnterior Basement Membrane Puncture

– 20-gauge needle–

FOREIGN BODIES

178

179

180

181

182

183

184

185

186

187

188

189

190

191

192

193

194

195

9/24/2013

22

CORNEAL/ CONJUNCTIVAL– HISTORY– TESTINGVA ( WITH AND WITHOUT PINHOLE)PUPILLARY STATUS

–ANISOCORIA–IRREGULAR SHAPE(OVAL)

–

Foreign BodiesSuperficial 65220, 65222, 65205, 67938Penetrating add 76529Perforating 76529, (65235)

FOREIGN BODIESPENETRATING

– LODGED IN TISSUE CAREFUL INSPECTION/ REMOVALREFERRALCT SCAN

PERFORATING– HISTORY IS CRITICAL– TRIAGE/REFER

Lids and AdnexaLacerations 870.0 99203, (67930)

– Hydrogen peroxide– Simple closure, topical and system antibiotic

196

197

198

199

200

201

202

203

204

205

206

207

208

209

210

211

9/24/2013

23

– Tetanus toxoid–

Ecchymosis 921.0Ptosis 374.3 92081, 92285NB: Supplemental procedures must be documented on separate forms.

Anterior Segment ProceduresCodes:

– Corneal Debridement: 65435 / $91.25– Penetrating FB: 65222/ $79.07– Corneal FB: 65222/

Keys to Success in Complex Viral DiseaseBetadine ProphylaxisPseudomembrane DebridementStromal HSKIridocyclitic HSKRecuurent HZK

Epidemic KeratoconjunctivitisEKC

– Serotypes 8,19 most typical– Seasonal – Primarily bilateral– Atypical serotypes; Enterovirus 70

Clinical Presentation– Chemosis– Injection– Infiltrates– Ac/reaction?– FBS–

EKCTreatments

– PalliativeCold compressTears

– InterventionalAnti-inflammatory agentsDecongestantsCombination agentsCidofovirBetadine

212

213

214

215

216

9/24/2013

24

Zirgan?

EKCTreatments

– Betadine wash– Surgical Debridement

Off-Label Adenoviral Treatments

EKC Betadine ProtocolTopical anesthetic x 2Non Alcohol betadine applied to inferior/ superior cul de sacOne minute waitRinse with artificial tearsApply Topical steroids x 3-4 in post treatment period

EKC Betadine ProtocolClinical “Pearls”

– Most effective if treated within 3 days of onset– Less effective in advanced cases– SPK incidence is close to 100%– Patients will complain of FBS 1-2 hours later–

ZIRGAN®

(ganciclovir ophthalmic gel) 0.15%FDA approval 9/16/2009Available in Europe under the trade name Virgan (Laboratoires Théa) since 1996Purchased from Sirion by Bausch & Lomb 2010

The Antiviral for the 21st CenturyZirgan 0.15% GelSirion PharmaceuticalsHSK 2 years and olderGanciclovir: Selectively targets replication of HSV DNA within corneal cellsDose: 5 x / day till lesion resolves then tid for one weekToxicity:

– 60% blur– 20% irritation– 5% Hyperemia

ZIRGAN® Mechanism of ActionActivated GCV inhibits the synthesis of viral DNA in 2 ways:

217

218

219

220

221

222

223

224

225

9/24/2013

25

(1) Competitive inhibitionActivated GCV directly inhibits viral DNA polymerase, preventing viral replication

(2) Chain terminationActivated GCV incorporates into viral DNA, preventing DNA synthesis

Adenovirus Conjunctivitis and keratoconjunctivitis caused by adenoviruses are common and highly

contagiousUsually affect both eyes and may cause epidemicsPatients may have painful conjunctival membranes and palpable preauricular

adenotherapy Zirgan is active in vitro against adenovirus as1

Tabbara did a controlled randomized double-masked clinical study of patients with adenovirus keratoconjunctivitis and found that ganciclovir significantly reduced both the duration of disease and the incidence of subepithelial infiltrates2

Adenovirus clinical trial (Tabbara, 2001)Controlled randomized masked series of 18 patients with adenoviral keratoconjunctivitis Compared treatment with GCV ophthalmic gel 0.15% versus preservative-free artificial

tearsMean time to recovery Significantly shorter for ganciclovir-treated patients: 7.7 days, in contrast to 18.5 days

for those receiving artificial tears (P < 0.05) Subepithelial opacities Developed in 7 (77%) patients treated with artificial tears, compared to 2 (22%)

patients in the GCV-treated group.

Herpes Simplex KeratitisIncidence and PrevalenceLeading cause of corneal blindnessAffects approximately 10 million people worldwide60% of the U.S. population shows evidence of infection by age 595% of the population by age 15Approximately 1% of infected patients develop ocular outbreaks20,000 new primary cases are diagnosed in the U.S. each year28,000 recurrences a year in the U.S.

ANTI-VIRALSCLINICAL APPLICATIONS

– ACUTE VS CHRONIC INFECTION– PRIMARY LESIONS– EPITHELIAL HERPES SIMPLEX– STROMAL HERPES SIMPLEX– HERPES ZOSTAR– HERPETIC IRIDOCYCLITIS

Oral AntiviralsIndications

226

227

228

229

230

231

9/24/2013

26

Infectious disease/ProphylaxisAcyclovir (Zovirax)Treatment 400mg 5x/d 1weekMaintenance 400mg 2x/d

Valaciclovir (Valtrex)Treatment 500 mg tid 1 weekMaintenance 500 mg qd

Famciclovir (Famvir)Treatment 250 mg tid 1 weekMaintenance 250 mg qd

Barron BA, Gee L, Hauck WW, Herpetic Eye Disease Study: A controlled trial of oral acyclovir for herpes simplex stromal keratitis. Ophthalmology 101: 1871-1882, 1994.

Oral Anti-viralsEffective against HSV and HZVTargets virally infected cells onlyInhibits DNA synthesis – activated by a virus-specific thymidine kinase then

phosphorylated by host enzymes into its active formFew side effects

– Nausea most common– Don’t use with diminished kidney function

Oral Antivirals Indications in Infectious HSV Endotheliitis Iridocyclitis Primary Herpetic DiseaseImmunocompromised patientsPost keratoplasty? All cases of Infectious

Epithelial Keratitis

ANTI-VIRALSSIDE EFFECTS

– RENAL FAILURE/ IMPAIRMENT

232

233

234

9/24/2013

27

– HYPERSENSITIVITY REACTIONS– FACIAL EDEMA– VISUAL HALLUCINATIONS

HSV Disease – RecurrenceRisk of Recurrence

– 25% recurrence risk over two years after a first episode of epithelial keratitis– Second episode has a 43% recurrence risk

Natural Course– Little scarring first recurrences– Scarring increases with increased recurrence– Vascularization– Stromal keratitis

Famvir (famciclovir)Pharmacology:

–Synthetic nucleoside (guanine) analog, prodrug of penciclovir. Penciclovir conversion into acyclovir triphosphate inhibits herpes virus-specific polymerases & produces viral DNA termination.

Formulation: –125, 250 and 500 mg tablets.

Usual Dosage:–Adults: 500 mg q8h x 7 days (HZV)–Children: Safety not fully evaluated.

Indications: –HZV ophthalmicus, suppression of recurrent HSV keratitis.Safety/efficacy of long-term HSV suppressive txnot fully established.

Zovirax (acyclovir)Pharmacology:

–Synthetic purine (guanosine) nucleoside analog. Acyclovir is phosphorylated by the enzyme thymidine

kinase which is encoded by herpes viruses (HSV-1, HSV-2, HZV). Acylovir triphosphate selectively

inhibits herpes-specific polymerase which, in turn, produces viral DNA termination.

Formulation: –400 and 800 mg tablets.

Usual Dosage:–Adults: 800 mg 5x qd x 7 days (acute HZV).–Children: Safety and efficacy not fully evaluted in ocular disease mgmt.

Indications:

235

236

237

238

239

9/24/2013

28

–HZV ophthalmicus, suppression of recurrent HSV keratitis.400 mg bid for up to 1 yr. for chronic suppressive tx. (greatest benefit in recurrent, vision threatening stromal HSV keratitis or cases where vision loss from HSV epith. keratitis is a concern).

Valtrex (valacyclovir HCl)Pharmacology:

–Synthetic purine (guanosine) nucleoside analog, prodrug of acyclovir. Valacyclovir is almost completely converted toacyclovir by first pass intestinal and/or hepaticmetabolism.

Formulation: –500 and 1000 mg tablets.

Usual Dosage:–Adults: 1000 mg q8h x 7 days (HZV).–Children: Safety not fully evaluated.

Indications: –HZV ophthalmicus, suppression of recurrent HSV keratitis.Safety/efficacy of long-term HSV suppressive tx not fully established, but likely comparable to acyclovir.

HSKSTROMAL KERATITIS

– RULE OUT MICROBIAL DISEASE– VIROPTIC– ORAL AGENTS– CORTICOSTEROIDS– CYCLOSPORINE A– SURGERYPKPCONJUNCTIVAL FLAPSTISSUE ADHESIVES

Herpes Stromal KeratitisOral acyclovir has demonstrated no benefit in the treatment of stromal keratitis1

Long term (one year) oral acyclovir reduces the risk of recurrent stromal keratitis2

240

241

242

243

244

245

246

247

248

9/24/2013

29

VARICELLA ZOSTAR- KERATITISPRIMARY INFECTION

– CHICKEN POX– VACCINATION RECOMMENDED BY AMERICAN ACAD of PEDIATRICS

RECURRENT INFECTION– OPHTHALMIC INVOLVEMENT 10-255– OPHTHLAMIC ZOSTAR > OVER AGE 60– UNDER 40 50% IIMMUNOCOMPRIMISED

Trauma ManagementBlow-Out Fracture

Blow-out FractureSymptoms

– Pain (especially on attempted vertical eye movement), local tenderness, double vision, eyelid swelling, crepitus after nose blowing

Signs– Restricted eye movement, subcutaneous or conjunctival emphysema, hypesthesia in

distribution of infraorbital nerve

Blow-out FractureTreatment

– Nasal decongestants– Broad-spectrum oral antibiotics for 7 days may be used but are not mandatory– Instruct patient not to blow nose– Apply ice packs to orbit for the first 24 to 48 hours– Surgical repair may be required

249

250

251

252

253

254

255

256

257

258

259

260

261

262

263

264

265

266

9/24/2013

30

Blow-out FractureFollow-up

– Review 1 and 2 weeks after trauma, evaluate for persistent diplopia or enophthalmos after acute oedema has subsided

– Monitor for associated ocular injuries, eg, orbital cellulitis, angle-recession glaucoma– Gonioscopy and dilated examination performed 3 to 4 weeks after trauma if hyphema

or micro-hyphema present

Thyroid Eye Disease

Thyroid Eye Disease (TED)Inflammation and enlargement of extraocular muscles, orbital and periorbital soft tissuesAutoimmune mediated phenomenonMost common with hyperthyroidism, though also seen in hypothyroid and euthyroid

states

Thyroid Eye Disease (TED)Generally presents in 4th – 6th decadeWomen 2.5-5x more frequently affectedMen usually affected more severely

MILD– Foreign Body Sensation– Redness– Tearing

MODERATE

– Pressure sensation– Puffiness of eyelids– Worsening ocular surface discomfort–

SEVERE– Double Vision– Dyschromatopsia– Visual field loss

SignsEyelid Retraction

– Most common and characteristic sign– Upper lid may “lag” behind the globe on down gaze– Lower lid retraction may be present as well

SignsOcular Surface Difficulties

– Injection over rectus insertions– Conjunctival Chemosis

267

268

269

270

2

271

2

272

273

2

9/24/2013

31

– Punctate Keratitis– Epiphora

SignsPeriorbital swelling with pronounced fat herniationProptosisLimitation of extraocular motility

Diagnostic StudiesThyroid function tests (TFTs)

– Patients with TED may have normal TFTs on presentationOrbital ultrasound or Orbital CT

– Enlargement of extraocular muscle bellies with normal appearing tendons– Inferior rectus > Medial > Superior > Lateral

Management OptionsMILD

-Artificial tears,especially with reading or computer work-Ointment at bedtime

Management OptionsModerate:

– Ramp up daily lubrication– Consider topical steroids– Encourage moisture chamber at bedtime– Consider surgical options

Management OptionsSevere: Double vision, Corneal Exposure, Optic Neuropathy

– Maximize lubrication for corneal issues– Short term options: Radiation, Steroids– Definitive Management:

1. Orbital Decompression2. Strabismus Surgery3. Eyelid Retraction Repair

Uveitis Made SimpleLaboratory testing

– Medical workup protocols

Medical Laboratory Work-UpIndications

BilateralRecurrentChronicUnresponsive to treatment

274

2

275

276

1

277

1

278

279

280

281

9/24/2013

32

Posterior uveitisPediatric uveitis (under age 15)

Medical Laboratory Work-UpPediatric - standard tests

– Erythrocyte sedimentation rate (ESR)– Antinuclear antibody (ANA)– ELISA or IgG/IgM for toxoplasmosis– ELISA or IgG/IgM for lyme– FTA-ABS– VDRL or RPR

Medical Laboratory Work-UpPediatric – TORCH if suspect infection or have posterior segment involvementTORCH Workup

– Toxoplasmosis– Other (Syphilis, Lyme)– Rubella– Cytomegalovirus (CMV)– Herpes simplex (HSV)

Medical Laboratory Work-UpAdult - standard tests

– Complete blood count (CBC) with differential– Erythrocyte sedimentation rate (ESR)– Antinuclear antibody (ANA)– FTA-ABS– RPR or VDRL– Lyme ELISA or IgG/IgM– PPD– Chest X-ray–

Medical Laboratory Work-UpAdult - additional tests to consider depending on medical history & symptoms

– Angiotension converting enzyme (ACE)– C Reactive Protein (CRP)– Lysozyme– HLA-B27– Rheumatoid Factor– ELISA or IgG/IgM for Toxoplasmosis– S-I Joint X-ray

Medical Laboratory Work-UpStandard test panel designed to detect some of the more commonly related systemic

diseasesMay add or substitute tests at clinician’s discretionShould design test strategy based on suspected diseases, not just order every possible

testUnless patient has pulmonary symptoms, may delay chest x-ray until receive the results

282

283

284

285

286

9/24/2013

33

from other tests• Need to evaluate both patient’s symptoms and laboratory values

Medical Laboratory Work-UpOther considerations

– Order ACE for all African/Caribean American patients– May need to consider other infectious disease titers depending on history– Important to remember that many tests are nonspecific even though they may be

abnormal in presence of systemic disease– Also possible to have normal or minimally elevated values for a particular test even in

the presence of inflammatory disease

Medical Laboratory Work-UpNonspecific Tests for Inflammation

– ESRElevated in systemic inflammation

– ANAIf detected, may indicate autoimmune disease

– CRPEnzyme produced in liver, elevated in systemic inflammation, may indicate risk for heart disease

– LysozymeEnzyme with antibacterial properties, may be elevated in bacterial infections

Medical Laboratory Work-UpDisease – Test Relationships

– Rheumatoid arthritis (ANA, ESR, CRP, RF, HLA-B27)– Systemic lupus erythematosus (ANA, CRP, ESR)– Giant cell arteritis (ESR)– Ankylosing spondylitis (S-I joint X-ray, HLA-B27)– Inflammatory bowel (HLA-B27)– Reiter’s syndrome (HLA-B27, joint X-rays)– Syphilis (FTA-ABS, VDRL or RPR)

Medical Laboratory Work-UpDisease – Test Relationships

– Sarcoidosis (ACE, chest X-ray, serum lysozyme, Gallium scan, biopsy)– Tuberculosis (PPD, chest X-ray)– Lyme disease (ELISA, IFA, IgG/IgM)– Toxoplasmosis (ELISA, IFA, IgG/IgM)– Toxocaris (ELISA, IgG/IgM)– Histoplasmosis (no accurate tests)– Herpes simplex (viral cultures, IgG/IgM)

Medical Laboratory Work-UpDisease – Test Relationships

– Varicella-Zoster (IgG/IgM)– Allergy (skin test, immunoglobulin levels)

287

288

289

290

291

9/24/2013

34

– HIV/AIDS (ELISA, western blot)– Behcet’s disease (HLA-B5)– Vogt-Kayangi-Harada syndrome (HLA-DR4)

AugmentinAmoxacillin/ClavaulanateBroad spectrum penicillin (Staph, Strep, HemophilusEffective against penicillinase producers-clavulanate blocks penicillinase@@@High therapeutic indexBacteriocidalLow GI side-efffectsSafe in pregnancyWatch out for allergyCheap***

292