Retinal Disease: What the Periphery Holds. Jeffry D. Gerson, O.D., F.A.A.O.

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1 Retinal Disease: What the Periphery Holds Jeffry D. Gerson, O.D., F.A.A.O.

2 Disclosure I have been on advisory boards/a consultant to/received honoraria from/ or been on speakers bureau list of the following: Allergan, Alcon, Arctic Dx, Bausch & Lomb, Freedom Meditech, Kemin, Maculogix, Optos, Optovue,Thrombogenix, VSP, ZeaVision These affiliations will have no affect on the content of this lecture

3 How do we see it? I love technology, but Don t forget about clinical exam 20D Slit lamp w lens Scleral depression Consider reclining

4 What is the periphery? Basic Anatomy Central Retina Foveola Fovea Para Fovea Peri fovea Macula Peripheral Retina Near Mid Far Ora Serrata

5 What is this in real life and does it matter? xxxxxxxxxx

6 How much is going on here? Not much until.. Any Concern?

7 Country - 22 Australia Bosnia Brazil Canada China Croatia Denmark England France Germany Iceland India Ireland Japan Korea Netherlands Philippines Portugal Saudi Arabia Scotland Spain 7 USA The Importance of the Periphery Increasing our Clinical Evidence Disease - 36 AMD Alzheimer's Autosomal Recessive Inherited Retinal Disease Birdshot Choroidal Melanoma Choroidal Nevus DME DR Epiretinal Membrane Glaucoma Healthy Hemangioma Hydoxychloroquine toxicity incontinetia pigmenti Lebers Macular Dystrophy Macula hole Malattia Leventinese MEWDS Multifocal Choroiditis Optic neuropathy Retinal Lesions Retinal Necrosis Retinal Vasculitis retinoschisis RP ROP RVO Retina Detachment Scotoma Stargardts Tumors Uveal Melanoma Uveitis Vitreoretinal pathology Vitreoretinal lymphoma

8 What does this mean to you?

9 What do you think 44yo healthy Used to have prediabetes but cured w lifestyle modifications MD not concerned

10 Now what do you want to know? In office RBG 463 In office A1c: >13 Unable to go to PCP today or tomorrow due work schedule Went to PCP 2 days later and started on Janumet I always try to f/u on this type of pt

11 3 months later. Came in for retinal f/u Retina unchanged Now on 2 meds for T2DM w dramatically changed outlook on disease EYE EXAM MADE THE DIFFERENCE!

12 If you don t think DM is a problem

13 Not only can we find the disease early We can and have to know who is at greatest risk of vision loss We can and have to identify those more at risk of CV Dz and stroke Sick eyes are in sick patients.and sick eyes aren t always sick in the macula

14 Diabetic Retinopathy ETDRS 7 Standard Fields Fundus Camera Views The gold standard for the current detection and classification of diabetic retinopathy is stereoscopic color fundus photographs in 7 standard fields, as defined by the Early Treatment Diabetic Retinopathy Study (ETDRS) group. Recent research has established the importance of monitoring the retinal periphery (area outside of ETDRS) for the progression of diabetic retinopathy.

15 ETDRS 7 fields vs UWF

16 Silva et al. Peripheral DR and Severity. Ophth. DR in the periphery To properly grade DR, you need to see the periphery Up to 10% of pts will have more severe DR when periphery considered vs standard 7-field photography Temporal was most important field Peripheral DR No DR in macula

Can periphery predict worsening? Outcome: 2 step progression or to PDR Primary peripheral lesions (PPLs) = 3.2x risk of progression 4.7x risk to go to PDR(25%!

17 Can periphery predict worsening? Outcome: 2 step progression or to PDR Primary peripheral lesions (PPLs) = 3.2x risk of progression 4.7x risk to go to PDR(25%! Of PPL to PDR!!) Independent of duration, A1c, age, gender, type or baseline severity More areas of PPL = more likely to progress Silva et al. PLs on UWF and progression. Ophth. 3/15

18 Is DME a macular disease? Or is it a macular manifestation of peripheral non-perfusion/pathology? Chronic vs acute The same thing is potentially happening in periphery as as posterior pole Could UWF FA help determine tx needed?

19 Does UWF FA offer value Proof of concept study shows can do less PRP and adjunctive anti- VEGF as Tx for poor perfusion to decrease need for injections Could less do more??

20 Is total PRP needed???

Diabetic Retinopathy Severity and Peripheral Lesions Are Associated with Nonperfusion on Ultra widefield Angiography The presence of peripheral lesions is associated with increased nonperfusion area

The data from our current study provide UWF angiographic evidence to support this hypothesis further and the long-held observation that nonperfusion in DR begins in the midperipheral retina and

21 Diabetic Retinopathy Severity and Peripheral Lesions Are Associated with Nonperfusion on Ultra widefield Angiography The presence of peripheral lesions is associated with increased nonperfusion area and nonperfusion index These findings were not correlated with macular edema or visual acuity and remained significant after adjusting for DR severity and diabetes duration. The data from our current study provide UWF angiographic evidence to support this hypothesis further and the long-held observation that nonperfusion in DR begins in the midperipheral retina and ischemia, thus accounting for the increased risk of progression. This approach [color ETDRS photos] generally remains the current standard of care in the management of DR. However, substantial advances in eye and medical care have improved visual and anatomic outcomes for many patients with diabetes and have shifted the focus from intervening only at advanced stages of disease to diagnosing and managing earlier stages of DR to potentially slow progression or prevent DR development. Reference: Aiello et al. Diabetic Retinopathy Severity and Peripheral Lesions Are Associated with Nonperfusion on Ultrawide Field Angiography Ophthalmology, 2015

22 The faces of DR.. Images compliments of J. Cavallerano, O.D.

23 When it goes bad Eyenet. 7/15

24 Bottom line of periphery and DR..Accumulating evidence suggests that UWF imaging identifies findings in the retinal periphery that may substantially improve rates of DR detection, better characterize DR severity and more accurately define risk of DR progression.. may support a need to redefine our current DR severitly classification systems to inforporate the new findings and thus improve the ability to predict natural history of DR and guide therapeutic interventions Sun JK and Aiello LP in JAMA Ophthalmology 12/2015

25 Retinal Breaks Flap or Horseshoe tear Operculated hole Atrophic hole Macular hole Dialysis Giant retinal tear

26 Retinal Holes Can occur anywhere Generally no treatment, unless symptomatic Rarely progresss to RD Pigmentation sign of chronicity PVD protective

27 Retinal Tears Up to 15% of symptomatic PVD will develop tear **What do you do about symptomatic tear? Refer for treatment

28 Tear Treatment Symptomatic tears require laser treatment Before and after Why treat symptomatic Approx 50% untreated will develop RD Approx 5% treated still develop RD

29 Retinal Detachments 2 day history of inferior blind spot 20/30 vision Superior tear Macula on or off? Intervention? 1mo after surgery, 20/25

30 Superior RD with single break 25 year old male with no symptoms, superior break, 20/20 vision and clear lens Treatment options?? Principles of treatment Retinal coagulation Scleral buckle Vitrectomy Pneumatic retinopexy

31 Pneumatic Retinopexy First introduced in late 1980 s Indications: Superior 8 clock hours of retina with limited break(s) covering 1 clock hour Principle: Gas bouyant upward--tension closes break--rpe pump clears SRF---Laser to seal around tear Similar success to scleral buckle Importance of positioning

32 What s This???? RD with tear at 930 OD Gas Injected day before to tamponade Returned next (day of photo) to receive successful laser

33 R.D. cont. Superior temporal RD Pseudophakic Multiple breaks Debris in vitreous from inflammation Treatment?

low occurrence of PVR Allows for internal drainage

34 Primary Vitrectomy Better ineroperative sight of peripheral tears Controlled removal of vitreous Focused endo-laser Very low occurrence of PVR Allows for internal drainage Air/Fluid/Gas exchange for tamponade Excellent outcomes 25g Vitrectomy

35 Inferior Detachment Healthy 35yo male 20/25 vision with recent onset of flashes and superior curtain Clear Lens Diagnosis?? Dx: Inferior Detachment with macula on

36 Retinal Detachment Immediate intervention needed since macula on with good vision Cryotherapy applied at time of surgery to seal retinal break With bullous RD s, drainage performed

force to flatten retina Different materials can be used for buckle Buckle

37 Scleral Buckle First performed in 1951 Traction pulls along downslope of buckle to create radial force Change in eye contour creates new tangential force to flatten retina Different materials can be used for buckle Buckle minimally visible externally normally Potential complications PVR Buckle related

38 Scleral Buckle Unable to use gas tamponde with inferior break Scleral buckle surgery gold standard SB alone as effective as SB +PPV in cases of undetected breaks 1 Yellow area is scar from cryotherapy Salicone et al. Mangement of RD when No Break is found. Ophthalmology. 3/2006

39 What s this? Scleral Buckle extrusion Can cause diplopia, motility problems, changes to retina appearance, endophthalmitis Treatment: removal of buckle, culture, antibiotic treatment

Operculated holes sometimes Atrophic holes rarely Lattice

40 To Treat or Not to Treat Indications for treatment Horse-shoe tear almost always Dialysis almost always Operculated holes sometimes Atrophic holes rarely Lattice no holes rarely Retinal Detachment Macula On Macla Off Emergent Not emergent

benefit Found in 7-10% of people Approx 1% of

41 No treatment needed if assymptomatic Prophylactic laser Lattice Degeneration No definitive proof to benefit Found in 7-10% of people Approx 1% of Lattice patients develop RD Approx 2% if Lattice with holes

42 Why not treat all lattice? 20-30% of eyes with RD have Lattice Degen. 89% of RD s from affected eyes occur in areas of normal peripheral retina So How can you treat if you don t know where RD will occur Eyes with risk factors don t seem to have lower incidence of RD if treated 2-4% of treated eyes still have RD 1 Prophylactic laser did not prevent tear or RD in fellow eyes if no PVD present at time of tx: 94% still developed tears, 76% developed RD 2 True science teaches us to doubt, and in ignorance to refrain Claude Bernard 1. Evidence based Prophylactic. Wilkinson C. P. Ophthalmology 1/2000 Editorial by Norman Byer, M.D. in same issue 2. Chauhan et al. Failure of Prophylactic Retinopexy. Arch Ophth. 7/06

43 Can your retina get a concussion?

44 Acute care in the office 34yo cauc female Got hit in eye last night w volleyball No f/f noted Vision is good but blurred spot above No pain Ant seg normal

45 So what do you do about this???

46 Same patient, 1 wk later.

47 Where do you find AMD???

48 Mild macular drusen, with more impressive peripheral changes

49 Dry AMD: Is it active AMD

analysed and the study found: In 77% of patients, AMD

50 Reykjavik Eye Study 573 patients imaged at 12 year time period Color and AF imaging The peripheral retina was analysed and the study found: In 77% of patients, AMD related changes were visualised outside of the area of the Topcon photos 50

A Population-Based Ultra-Widefield Digital Image Grading Study for Age-Related Macular Degeneration Like Lesions at the Peripheral Retina (Reykjavik study) 570 subjects with AMD at 12 year follow-up

51 A Population-Based Ultra-Widefield Digital Image Grading Study for Age-Related Macular Degeneration Like Lesions at the Peripheral Retina (Reykjavik study) 570 subjects with AMD at 12 year follow-up Reykjavik Eye Study color and AF optomap imaging 13.6% had AMD-like changes in the macula alone 10.1% had changes in the periphery alone 57.4% had changes in both the periphery and macula Phenotyping the retinal periphery using the categories defined by the International Classification (75 degrees) confirmed the presence of wide-ranging AMD-like pathologic changes even in those without central sight-threatening macular disease. Based on our observations, we propose here new, reliably identifiable grading categories that may be more suited for population-based UWFI. Reference: Lengyel et al. A Population-Based Ultra-Widefield Digital Image Grading Study for Age-Related Macular Degeneration Like Lesions at the Peripheral Retina Ophthalmology, 2015

53 Case 6: Case Optomap Case 6: Optomap 6: plus Optomap with plus Resmax plus with Resmax with Green Resmax Separation Color FAF Fundus Image Fundus Image of Image Left of Eye Left of Eye Left Eye Note the hypo AF zone in the macula is surrounded by an area of hyper AF.. Hot spots At higher magnification the underlying choroidal vessels are more easily visualized corresponding to the surrounding hyper AF area indicate an increase in both metabolic activity and lipofuscin. within the macular lesion. Slide created by Jerome Sherman, O.D., F.A.A.O. *Courtesy of the Reykjavik Eye Study

the AF images are yielding additional information.

54 Case 6: Optomap plus with Resmax OS Note that the hypo AF lesions nasally do not correspond to the drusen and hence the AF images are yielding additional information. Link to RR 27 By Jerome Sherman *Courtesy of the Reykjavik Eye Study

55 More recent literature on FAF and AMD 3 distinct FAF patterns identified Granular, Mottled and Nummular 90% concordance between eyes More FAF in neovasc AMD vs dry vs normal 86% vs 73% vs 18% OR w wet AMD: 12.7 and Dry: 6.2 vs normal Older age and female also associated w more FAF Associations found between: Granular FAF and peripheral drusen Mottled FAF and RPE depigmentation Tan et al. Peripheral FAF in AMD. Ophth. 6/2013

56 FAF examples A: Peripheral drusen B. Granular FAF C. RPE atrophy D. Nummular FAF E. Periph RPE depig and finde drusen F. Mottled FAF at arrow, and fine FAF at drusen

57 ARVO poster: Domalpally et al. ARVO Ultra WF AF imaging in AMD: AREDS2 ancillary Study. FAF from AREDS2 OPERA: Optos Peripheral Retina (study within AREDS2) Looked for AF abnormalities in 3 zones: central, to vortex, and outside vortex Percentage w abnormalities by zone: 94/83/50% Some difference between superior and inferior periphery, but not significant Abnormalities in both advanced and non-advanced eyes

OPERA - Optos PEripheral RetinA AREDSII Sub-study Study objective: to study the correlation of reticular pigmentation, neovascularization, drusen, and geographic atrophy found at these two locations

58 OPERA - Optos PEripheral RetinA AREDSII Sub-study Study objective: to study the correlation of reticular pigmentation, neovascularization, drusen, and geographic atrophy found at these two locations within the retina color and AF optomap imaging 570 subjects enrolled in AREDSII trial - Results: Presence of Drusen: - 97% of eyes in Zone 2-77% of eyes in Zone 3 Super large drusen (>250µ): - 63% of eyes in Zone 2-39% of eyes in Zone 3 Presence of Choroidal Neovascularization in Zone 1: - 68% had peripheral reticular pigmentation in Zone 2-12% had cobblestone degeneration in Zone 2-55% had cobblestone in Zone 3 (superior) - 25% had reticular pigmentation in Zone 3 (superior) Documentation of such findings may have implications regarding the risk of visual loss in AMD patients. AMD is NOT confined to the posterior pole. Reference: Friberg et al. Peripheral Retinal Findings in color images in Age-Related Macular Degeneration. ARVO 2015.

59 So what really is AMD? A generalized retinal degeneration (present throughout the retina, especially in the periphery) that is visually significant due to changes in the retina

60 How does Optomap AF compare Comparison of Optomap AF to HRA FAF in CSCR. Shin et al. Graefes 12/15. OAF more effective than HRA in identifying area of Serous RD and also areas of mild outer retinal damage Since better at identifying margins, easier to detect changes over time OAF correlated well to not only anatomic changes, but also visual changes

61 What does RP really look like?

62 RP: 20/20- vision OU: impressive FAF!

63 Another RP: 20/25-, symptomatic

Debbie a patient for over 10yrs Vision approximately 20/100 and stable for years Always wondering if vision will get worse Some difficulties w

64 Debbie a patient for over 10yrs Vision approximately 20/100 and stable for years Always wondering if vision will get worse Some difficulties w job, but nobody at workplace knows of visual difficulties Drives w Bioptic and has for years What is the dx and can we tell if she is getting worse?

65 Stargardt s Dystrophy

Does Plaquenil toxicity always start in Especially in Asians, Pericentral presentation may be initial sign Pericentral only in Asians in approx.

66 Does Plaquenil toxicity always start in Especially in Asians, Pericentral presentation may be initial sign Pericentral only in Asians in approx. 12% 50% of Asians w toxicity, had at least some pericentral (vs 2% in Caucasians) By the way, how common is toxicity: 1%/2%/20% at 5/10/20 yrs macula?

67 So, does the periphery matter? Peripheral retinal examination matters for not only peripheral only pathology, but also things that are thought of as macular only. Macular disease is often present in the periphery The periphery may be the first sign of disease Comparison from 1 year to the next will show change over time

68 Thank You Jeffry D. Gerson, O.D., F.A.A.O.

Retinal Disease: What the Periphery Holds Jeffry D. Gerson, O.D., F.A.A.O.

Retinal Disease: What the Periphery Holds Jeffry D. Gerson, O.D., F.A.A.O. jgerson@hotmail.com Disclosure I have been on advisory boards/a consultant to/received honoraria from/ or been on speakers bureau