New Technologies in Glaucoma Management: From ERG to OCT

Transcription

1 What s New and What s Next in Glaucoma New Technologies in Glaucoma Management: From ERG to OCT Ben Gaddie, OD FAAO Murray Fingeret, OD FAAO IOP 24- Hour IOP Role of hysteresis in glaucoma risk Cerebrospinal fluid pressure and IOP Optic Nerve/RNFL/Posterio r pole What changes first RNFL or optic nerve or macula Confocal Scanning Laser Ophthalmoscopy improved form of retinal photography Advances in Optical Coherence Tomography Flipping the TSNIT What s New and What s Next in Glaucoma Visual fields Role of central fields in diagnosing and monitoring glaucoma Incorporating fields with imaging IOP Normally Fluctuates Throughout the Day and Night IOP normally exhibits a circadian rhythm Larger range of IOP in glaucoma patients than in control subjects Damage might occur IOP whenever IOP is elevated Large diurnal IOP fluctuations may be a risk factor for disease progression Normal individual Glaucoma patient 12 AM 12 PM Time 12 AM Permanent Continuous Monitoring Provide daytime and nighttime IOP measurements through self-contained implant Accessed remotely with wireless technology Ideal for advanced glaucoma Would not be measuring the surface but rather taking IOP measurements directly inside the eye Subject to less noise Permanent Continuous Monitoring Recent idea is incorporating telemetric IOP device with IOL Digital signal would be sent form IOL to eyeglasses worn by patient Alarm raised at certain point Long-term stability is unknown 1

2 Continuous IOP Monitoring How do we evaluate IOP if we are only measuring it briefly in office? Three approaches to measure IOP over 24 hour period Self tonometry Permanent continuous IOP monitoring Temporary continuous IOP monitoring Self Tonometry Patients would monitor their IOP over time with easy-to-use devices Easiest approach in regards to continuous monitoring Adapt current device such as Noncontact tonometer or Rebound tonometer May be difficult for some patients to peform May be Not easy to obtain 24 hour IOP Temporary Continuous Monitoring Non-invasive contact lens based systems that measure IOP over hour period Recognize IOP fluctuations which may be significant Silicone contact lens which has strain gauge must fit tight to reduce noise Corneal health issues with tight lens Problems with noise, discomfort Sensimed system in use in Europe that has contact lens, antennae system and recorder Not available in US Triggerfish Contact Lens 24- Hour IOP Monitoring Device Leonardi M, et al. Wireless contact lens sensor for intraocular pressure monitoring: assessment on enucleated pig eyes. Acta Ophthalmol. 2009: 87:

3 Triggerfish Contact Lens IOP Device The lens is designed to provide a more accurate assessment of IOP Lens worn for 24 hours and discarded Consists of a clear, silicone contact lens ringed by a strain gauge and a microprocessor and antenna that transmits data to an external receiver The gauge continuously monitors the shape of the cornea, indicating greater or lesser intraocular pressure Information about IOP fluctuations is immediately transmitted via radio frequencies from the lens microprocessor to a recording receiver The microprocessor is powered by an induction loop which uses a magnetic field around the eye to generate the tiny amounts of required electricity Induction loops are also used to power hearing- aid implants Comparison to 24-hour IOP profile in UCSD sleep lab Mosaed, Liu, Weinreb. Correlation between office and peak nocturnal IOP in healthy subjects and glaucoma patients. AJO 2005;;139:320-4 Self Tonometry Patients would monitor their IOP over time with easy-to-use devices Easiest approach in regards to continuous monitoring Adapt current device such as Noncontact tonometer or Rebound tonometer May be difficult for some patients to perform Not easy to obtain 24 hour IOP 3

4 Temporary Continuous Monitoring Non-invasive contact lens based systems that measure IOP over hour period Recognize IOP fluctuations which may be significant Silicone contact lens which has strain gauge must fit tight to reduce noise Corneal health issues with tight lens Problems with noise, discomfort Sensimed system in use in Europe that has contact lens, antennae system and recorder Not available in US 4

5 Triggerfish Contact Lens IOP Device The lens is designed to provide a more accurate assessment of IOP Consists of a clear, silicone contact lens ringed by a strain gauge and a microprocessor and antenna that transmits data to an external receiver The gauge continuously monitors the shape of the cornea, indicating greater or lesser intraocular pressure Information about IOP fluctuations is immediately transmitted via radio frequencies from the lens microprocessor to a recording receiver The microprocessor is powered by an induction loop which uses a magnetic field around the eye to generate the tiny amounts of required electricity Induction loops are also used to power hearing- aid implants Triggerfish Contact Lens IOP Device Worn for just 24 hours, then discarded Obtain a detailed description of the patient s IOP and eye health It s the difference between seeing a single movie frame and watching a full- length motion picture Better understand what is happening to the eye, providing earlier and more accurate diagnoses Detect changing conditions and adjust or alter treatments more effectively Personalized medicine for the eye Corneal Hysteresis Reichert instrument based upon the noncontact tonometer Measures corneal response to indentation by rapid air pulse Measures pressure peak at applanation (IOP 1) and Pressure when cornea becomes flat (IOP 2) Difference between two pressures is termed corneal hysteresis Measure cornea biomechanical properties Applanation Signal Plot Corneal Hysteresis Rigidity of cornea may be associated with the risk of glaucoma development Reichert instrument based upon the non-contact tonometer Measures corneal response to indentation by rapid air pulse to determine viscoelasticity Reduced hysteresis associated with increased risk Measures Pressure peak at applanation (IOP 1) and Pressure when cornea becomes flat (IOP 2) Difference between two pressures is termed corneal hysteresis Measure cornea biomechanical properties 5

6 Cerebrospinal Fluid Pressure (CSF) and Glaucoma Recent work shows that low CSF may be contributory to the development of glaucoma Trans laminar pressure differential IOP, CSF Could explain pathogenesis for normal tension glaucoma What s New and What s Next in Glaucoma Optic Nerve/RNFL/Posterior pole What changes first RNFL or optic nerve or macula area Confocal Scanning Laser Ophthalmoscopy improved form of retinal photography Advances in Optical Coherence Tomography Structure- function correlations Flipping the TSNIT 6

7 What s New and What s Next in Glaucoma Optic Nerve/RNFL/Posterior pole What changes first RNFL or optic nerve or macula area Confocal Scanning Laser Ophthalmoscopy improved form of retinal photography Advances in Optical Coherence Tomography Structure- function correlations Flipping the TSNIT What Changes First The RNFL or The Macula Area or the Optic Disc? OCT TECHNOLOGY: SPECTRAL DOMAIN Spectral domain OCT (also called Fourier- domain or high- definition OCT) was FDA approved in 2006 Spectral domain OCT uses a stationary reference arm and eliminates the need for a moving mirror; it does so by using a spectrometer as a detector Swept Source OCT Swept- source (SS) OCT is a next- generation Fourier domain OCT that demonstrates less signal decay over depth compared with the current SD OCT. Faster speed Probe light with a center wavelength of 1040 to 1060 nm, which allows high- penetration imaging deep retinal tissues such as Choroid and Sclera SS OCT improves visualization of the deep structures of the optic disc Compared with SD OCT, SS OCT is characterized by a higher speed scan rate and relatively lower sensitivity roll- off versus depth Swept Source OCT 100,000 A scans per second w 1 micron wavelength lightsource (1050 nm) Deep Tissue Imaging Penetrates deeper into retina for choroid and lamina assessment Images through cataracts Swept source OCT is faster because: No spectrometer No line- scan camera (for detector) Utilizes tunable laser source Sweeps across spectrum rapidly Photodiode detector (near instantaneous) Macula Testing in Glaucoma Imaging to detect glaucoma damage has concentrated around RNFL and optic nerve evaluation Complicating the assessment of the optic nerve when evaluating for glaucoma damage is: High variability of the ONH size and shape Even among healthy individuals Wide range of optic cup shapes and sizes Variable size and configuration of blood vessels Variable angle of penetration into the eyeball of the optic nerve (tilted disc) Parapapillary changes such as atrophy These are the reasons why it is difficult to detect early glaucomatous damage 7

8 Macula Testing in Glaucoma Imaging allows measurement of features that are not possible otherwise Imaging can detect changes in the macular region The eye has about 1 million retinal ganglion cells, and their numbers are densest in the macula about six cells deep About 50% of ganglion cells are in the central 4.5 mm of the retina an area that represents only 7% of the total retinal area This area is not well covered in most visual field testing What is EDI? Enhanced Depth Imaging For spectral domain, sensitivity is highest at top of window (vitreous) and declines with depth With EDI, sensitivity in window is flipped and now sensitivity is higher on bottom (lamina or choroid) Loss of sensitivity at top (vitreous) Advantage of swept source is less drop off in sensitivity with depth of imaging All OCTs have ability to shift sensitivity with depth Enhanced depth imaging (EDI) Enhanced depth imaging (EDI) was developed for SD OCT to improve image quality of the deep structures of the posterior segment However, although EDI is an effective method for visualizing the deep structures of the optic disc, it is disadvantageous for observing axially extended structures in highly myopic eyes in their entirety because its signal intensity decays with axial distance. The Structure- Function Problem in Glaucoma RNFL loss frequently detected before visual field change One way to correct problem and be able to detect change earlier by using a linear scale on perimeter Advantages of Flipping the RNFL TSNIT was an arbitrary designation 25 years ago Temporal region is mos t important part of curve and with NITSN, region is not broken up and loss more obvious Easier to recognize structure- function correlation RNFL loss correlates easily with field loss Easier to understand if macula area may be involved and central field loss present Is there a reduction in RNFL within the central 8 0 OCT First generation Time Domain Second generation Spectral Domain Next generation Swept Source 8

9 What Changes First The RNFL or The Macula Area or the Optic Disc? What is the Best Tool to Detect Glaucomatous Damage? The inferior Temporal Portion Of The Optic Disc is Most Vulnerable 1. Hood DC et al. PRER 2013:1-25 9

10 Optic Disc Analysis How Does An OCT Measure the Optic Disc Size? What boundary is used for the disc edge? Retinal pigment epithelial tips OR Bruch s Membrane Opening (BMO) Use BMO New parameter- Minimal Rim Width (MRW) to evaluate neuroretinal rim Both Cirrus and Spectralis use this metric Line drawn perpendicular from BMO to surface Advantages of Flipping the RNFL TSNIT was an arbitrary designation 25 years ago Temporal region is mos t important part of curve and with NITSN, region is not broken up and loss more obvious Easier to recognize structure- function correlation RNFL loss correlates easily with field loss Easier to understand if macula area may be involved and central field loss present Is there a reduction in RNFL within the central 8 0 Macula Testing in Glaucoma Imaging to detect glaucoma damage has concentrated around RNFL and optic nerve evaluation Complicating the assessment of the optic nerve when evaluating for glaucoma damage is: High variability of the ONH size and shape Even among healthy individuals Wide range of optic cup shapes and sizes Variable size and configuration of blood vessels Variable angle of penetration into the eyeball of the optic nerve (tilted disc) Parapapillary changes such as atrophy These are the reasons why it is difficult to detect early glaucomatous damage Macula Testing in Glaucoma Imaging allows measurement of features that are not possible otherwise Imaging can detect changes in the macular region The eye has about 1 million retinal ganglion cells, and their numbers are densest in the macula about six cells deep About 50% of ganglion cells are in the central 4.5 mm of the retina an area that represents only 7% of the total retinal area This area is not well covered in most visual field testing 10

11 Measuring the ganglion cell complex directly (ILM IPL) Inner retinal layers and provides complete Ganglion cell assessment: Nerve fiber layer (g- cell axons) Ganglion cell layer (g-cell body) Inner plexiform layer (g-cell dendrites) What is EDI? Enhanced Depth Imaging For spectral domain, sensitivity is highest at top of window (vitreous) and declines with depth With EDI, sensitivity in window is flipped and now sensitivity is higher on bottom (lamina or choroid) Loss of sensitivity at top (vitreous) Advantage of swept source is less drop off in sensitivity with depth of imaging Valuable to examine lamina cribosa visibility All OCTs have ability to shift sensitivity with depth Images courtesy of Dr. Ou Tan, USC Enhanced Depth Imaging (EDI) Without EDI With EDI Vitreous / Retinal interface highlighted Bruch s membrane opening (Neural Canal Opening - NCO) Blood Flow Measurements using Spectral Domain OCT OCT Angiography Anterior surface of lamina cribrosa Posterior surface of lamina cribrosa Measuring Blood Flow Ocular blood flow and optic nerve injury have been linked The question still not answered is which comes first Can a device be developed that provides reproducible, quantitative, objective assessment of retinal and optic nerve blood flow Both global and local Does not require expert operator Measurement should correlate with structure and function 11

12 Measuring Blood Flow There have been numerous devices to measure blood flow over the years Varying degrees of invasiveness, accuracy and precision From injectable dyes to ultrasonography to laser Poorly reproducible or variations in acquisition of data Optical Coherence Tomography Angiography Used to map retinal and superficial optic nerve vasculature and blood flow Not clear if there is a floor effect Is technique useful from early to advanced disease? OCT and Progression SDOCT measurements are highly reproducible. 2-4 Steps in Range Just like perimetry, the average patient can lose a third of his/her RNFL or neuro- retinal rim and still be inside the OCT normal range. Normal ranges for Average RNFLT 95th percentile = 107 microns 50th percentile = 89 microns 5 th percentile = 75 microns We can measure multiple steps of statistically significant change while a glaucoma suspect still is in the green normal range. Normal significance Limits for Average RNFLT 95th percentile = 107 microns 50th percentile = 89 microns 5 th percentile = 75 microns 1 st percentile = 67 microns 1 st percentile = 67 microns Risk of Disability <50 microns Leung et al. Ophthalmology 2009;116:1257 Roh et al. Ophthalmology 2013;120:969 Wong et al. OptomVis Sci 2014;92 Matlatc h et al, IOVS Sep Risk of Disability <50 microns 1 Carl Zeiss Meditec. Cirrus HD-OCT : How to read the Ci rrus Reports.. Values shown are for a 69 year old normal. 1 Values shown are for a 69 year old normal. 12

13 New Imaging Devices Confocal Scanning Laser LCD Camera Fundus Photographs are Getting Better Centervue Eidon Confocal Scanning LCD Scanning Laser Ophthalmoloscopic systems are superior to conventional fundus cameras as they exploit confocal imaging principle limits the effect of backscattered light from deeper layers and provides enhanced image quality Another advantage of SLO systems is that they operate with smaller pupils than conventional fundus cameras However, SLO systems do not provide color images, as they typically employ multiple, monochromatic, laser sources, resulting in black and white or pseudo- color images Different from existing SLO systems, EIDON uses WHITE light instead of monochromatic lasers providing true color imaging Compass Centervue Fundus Automated Perimetry Confocal scanning laser LED camera Focus on back of eye so no trial lens needed No trial lens defect Has eye tracking so fixation no longer an issue Can tell if ptosis is a problem by watching monitor in real time Shows back of eye and where targets are being presented Uses ZEST algorithm Longer than SITA What s New and What s Next in Glaucoma Visual fields Role of central fields in diagnosing and monitoring glaucoma Incorporating fields with imaging The Central Field in Glaucoma Diagnosis is based upon damage to the structural and functional system Functional loss may appear later in the testing sequence In regards to functional loss, damage may be present in the central or peripheral region Glaucoma is thought to affect the central field last as the condition gets worse Is this conventional wisdom true? 13

14 Is This Presentation Rare? The Central Field in Glaucoma Does the 24-2 detect functional vision loss in the central 10 0 in all cases? Points in test grid are 6 0 apart in a grid pattern Is there a role for a complementary test such as the 10-2 in which 55 points are placed in a 10 0 area that are 2 0 apart? Will this detect small scotomas that fall between the cracks? Is glaucoma a disease that involves the macula region early in the condition? Central Visual Fields and Glaucoma Recent papers have suggested that the 24-2 test pattern has limited ability to detect central field defects 50% of retinal ganglion cells are found within 4.5mm of fovea Macula region comprises only 10% of overall visual field area though it is responsible for 60% of area of visual cortex Damage to central 10 0 associated with diminished contrast sensitivity, reduced reading ability 14

15 Can the 24-2 Test Pattern Be Modified to Improve Detection of Glaucoma Field Defects? The Structure- Function Problem in Glaucoma RNFL loss frequently detected before visual field change One way to correct problem and be able to detect change earlier by using a linear scale on perimeter Objective Functional Testing Visual Evoked Potentials/Electroretinogram Diopsys, Konan Elicit functional information without patient involvement 15