Case cont. SLE: OD only, OS prosthetic LLL: Mild dermatochalasis, trace lash debris C/S: White and quiet, with inferior palpebral concretions OS: Debris in tear film on surface of prosthesis K: Clear AC: Deep and quiet IRIS: Flat and intact LENS: +1 NS By Jessica Cameron, O.D. 61 y/o white male (June 2013) Case cont. CC: Patient presents for comprehensive exam with DFE. Last eye exam 2 years ago. PMH: Migraines, Parkinson Disease, Hypothyroidism, (-)DM, (-)HTN Current Meds: Propranolol HCL 80MG, Synthroid 0.125MG, Aspirin 81MG, Carbidopa25/Levodopa 100MG, Bupropion HCL 150MG POH: Prosthetic eye due to trauma OS, Choroidal nevus OD, Previously worked up as a glaucoma suspect with testing within normal limits DFE: OD only, OS prosthetic VITR: Extensive syneresis without PVD C/D: 0.6h/0.5v P&D intact rim tissue A/V: 2/3, tortuous vessels MACULA: See Figure 1 PERIPHERY: Intact 360, choroidal scarring sup/temp and vitreous condensation inf/temp 1.25 DD nevus inf (-)fluid (-)drusen (-) Holes/Breaks/Tears 360 Other history to be disclosed later Case cont. MRx: Right eye: -1.50 +0.25 x 110 20/80 +/- PH: 20/NI LV: 20/30+/Left eye: Balance 20/NLP Add: +2.00 NVA: 20/40+ @ 40 cm Prelims: Pupils: OD: Round, reactive, Dim: 3.5mm Light: 2.5mm EOMS: FROM OD, slight movement of prosthetic OS Goldmann Tonometry time: 11am Right eye: 18 Left eye: - Amsler Grid: OD: (-) scotoma, (+) metamorphopsia of the superior right and left sides of grid Figure 1 Classification by JDM Gass Differentials Stage 1: 20/20-20/60 Stage 2: 20/40-20/100 Stage 3: 20/60-20/200 Macular Hole Macular Pseudohole Macular Lamellar Hole Intraretinal Cystic Changes of Macula Stage 4: 20/400-CF http://www.revophth.com/content/d/retinal_insider/i/1296/c/24953/ http://toptenfilms.net/309-back-to-the-future/ Research and Statistics Macular Hole Progression Stage 1 to full thickness (stage 3, 4) ○ Akiba et al – 37% ○ Guyer et al – 10.5% Symptoms – metamorphopsia, decrease in acuity, and central scotoma Signs – decrease in best corrected visual acuity (BCVA), positive watzke allen test Dilated Exam: exposed retinal pigmented epithelium seen Stage 2 to Stage 3 ○ Hikichi et al – 67%, with 30% to stage 4 on dilated exam Macular OCT: loss of foveal contour, full thickness hole • Watzke-Allen Test: narrow slit beam over the macula, patient describes what he or she perceives Risk of fellow eye Without PVD, 5 year risk: 10-12% With PVD present <1% http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v6/v6c061.html Causes… Research and Statistics Cont. Traction Spontaneous Closure Stage 1 holes resolve 30-50% http://retinagallery.com/displayimage.php?pid=3401 Epiretinal membrane Stage 2 or 3 lesions have a rare chance <10% Closure is associated with vitreofoveal separation or Trauma Idiopathic full PVD Anatomically holes are sealed by proliferative glial cells on surface of the retina and Müller cells at intraretinal edges http://westbocaeye.com/?attachment_id=138 http://www.rethinkvmt.com/progression.shtml Macular Lamellar Hole Review of Retinal Layers “lamella” - A thin layer or sheet Macular tissue that has lifted from the remaining tissue, with cleft between outer and inner retina Possible precursor to full thickness hole Relatively preserved visual acuity ○ 20/40 or better Overlap in literature Accompanied by ERM Similar mean VA to Pseudohole Absence of Full Thickness defect http://www.optomcpd.com/14.html http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c021.html http://www.retinalphysician.com/articleviewer.aspx?articleid=100221 Intraretinal Cystic Changes of Macula Review of Retinal Layers Break down of inner blood-retinal barrier affecting outer plexiform layer and the inner nuclear layer Fluorescein angiogram shows the classic 'petaloid' leakage of dye (hyperfluorescence) Causes: Retinal Vascular Leakage Diabetic retinopathy Branch retinal vain occlusion Pseudophakia or aphakia Idiopathic retinal telangiectasia Choroidal neovascularization Without Retinal Vascular Leakage Certain types of retinitis pigmentosa Early stages of macular hole Nicotinic acid maculopathy Treatment: Steroids and NSAIDs, Visudyne with nonthermal diode laser, Focal Laser Photocoagulation, Anti-VEGF drugs, Micropulse laser http://www.studyblue.com/notes/note/n/retina/deck/2737346 Macular Pseudohole Back to our Case: Macula OCT Macular tissue still has full thickness visual acuity is usually good (20/20-20/30) June 2013 possible metamorphopsia VA: 20/80+/- Examples: Macular pucker induced by ERM Solar retinopathy http://www.nyee.edu/aric_spectral.html?large_print=1 http://shop.onjoph.com/catalog/product_info.php?products _id=6708&language=en Back to our Case: Macula OCT Restored Photoreceptor Outer Segment and Visual Recovery After Macular Hole Closure Sano et al - 2009 retrospective case study, 28 eyes one, three, and six months post operatively using spectraldomain OCT 4 Patterns of OCT findings Stage 3 Macular Hole 1. Continuous IS/OS line 2. Continuous IS/OS line with outer foveal defects 3. Disrupted IS/OS line 4. Disrupted IS/OS line with outer foveal defects 1 2 3 4 Consult sent to Ophthalmology Treatment Sano et al - retrospective case study (cont) Observation - Pseudohole, Lamellar Hole, Stage 1 Pars Plana Vitrectomy with ILM peel and gas tamponade - Stage 2-4 90% success rate Post-operative risks: retinal detachment, hemorrhage, intraocular infection, cataract formation, and others Complications: recurrence of macular hole Ocriplasmin (Jetrea®) - VMT Plasmin that hydrolyzes collagen, fibronectin and laminin The MIVI-TRUST study ○ 26.5% relieving traction Mean BCVA in each group Continuous IS/OS line ~20/32 Continuous IS/OS line with outer foveal defects ~20/25 Disrupted IS/OS line ~20/60 Disrupted IS/OS line with outer foveal defects ~20/80 Conclusion: IS/OS appearance was the only relevant factor affecting the postoperative VA at 6 months. Central foveal thickness and foveal abnormality were not significantly correlated with visual outcomes http://eastbayretina.com/vitrectomy#/page-20 http://www.karger.com/Article/Fulltext/104768 Success with surgical intervention Case from study: 64 y/o male stage 4 hole Pre-op VA: 20/50 Prognostic factors Ip et al - suggested a correlation between macular hole size and visual recovery ○ 92% closure of 24 eyes with macular holes smaller than 400µm ○ Only 56% of the 16 eyes with macular holes larger than 400µm ○ Conclusion: successful closure is associated with macular hole diameters smaller than 400µm and with length of visual symptoms less than 6 months Postoperative visual outcome is not always satisfactory even in eyes with anatomical success Cataract formation needing surgical intervention between 6-12 months after macular hole surgery With further improvement in visual acuity continued for 2-3 years after surgery Why do some patients regain visual function and others do not? 1 month post op - foveal detachment with disrupted IS/OS 6 months post op - outer foveal defect with continuous IS/OS line (VA: 20/20) Sano et al Case from study: 62 y/o male stage 2 hole pre-op VA: 20/200 NO surgical intervention 1 month post op - foveal detachment with disrupted IS/OS 6 months post op - outer foveal defect with disrupted IS/OS line (VA: 20/60) Sano et al Progression to Regression Back to our patient.. May 2011 VA: 20/30+/- September 2013 VA: 20/40-2 November 2013 VA: 20/30 Conclusion Patient presents 3 months later.. September 2013 VA: Right eye: 20/40-2 June 2013 VA: 20/80+/- LV: 20/80+/- DFE: Vitreous: Presence of PVD Macula: Trace erm, macular hole appearance, (-) CSME, (-) CNVM Improvement of watzke allen sign (thinning of line without break) Note from Opthalmology… Close observation of impending holes especially if present with VMT or ERM. Suggested Ophthalmology consult with stage 2 holes or if progressive vision loss Stage 2 or 3 lesions having spontaneous closure is LOW <10% Patient Case: Improving VA, Partial closure with inner joined retina, pending Ophthalmology consult http://www.ophthalmologymanagement.com/articleviewer.aspx?articleID=100598 References Hikichi T, Yoshida A, Trempe CL. Course of vitreomacular traction syndrome. Am J Ophthalmol. 1995;119:55-61. Gass JDM. Reappraisal of biomicroscopic classification of stages of development of a macular hole. Am J Ophthalmol. 1995, 119(6):752-759. Stalmans, Peter et al. Enzymatic Vitreolysis with Ocriplasmin or Vitreomacular Traction and Macular Holes. The New England Journal of Medicine 2012; 367: 606-615. Lorne B. Yudcovitch. Acquired Macular Diseases: Pathophysiology, Diagnosis and Management. http://www.pacificu.edu/optometry/ce/courses/18809/macdiseasepg2.cfm Sano, Morihiko et al. Restored Photoreceptor Outer Segment and Visual Recovery After Macular Hole Closer. Am J Ophthalmol. 2009; 147: 313-318. Kang SW, et al. Types of Macular Hole Closure and Their Clinical Implications. Am J Ophthalmol. 2003; 87:1015-1019. Yamashita T, Kishi S. Spontaneous Closure of Traumatic Macula Hole. Am J Ophthalmol. 2002; 133: 230-235. Takahashi H, Kishi S. Cross-sectional Images of Spontaneous Macular Hole Closure. Am J Ophthalmol. 1999; 128: 519-520. Selver OB et al. Spontaneous Resolution of Vitreomacular traction: a Case Series. Clin Exp Optom. 2013; 96: 424-427. Ezra E. Idiopathic Full Thickness Macular Hole: Natural History and Pathogenesis. Br J Ophthalmol. 2001; 85: 102-108. Chew EY, Sperduto RD, Hiller R, Nowroozi L, Seigel D, Yanuzzi LA, Burton TC, Seddon JM, Gragoudas ES, Haller JA, Blair NP, Farber M. Clinical course of macular holes: the Eye Disease Case-Control Study. Arch Ophthalmol. 1999;117:242-246. Morgan CM, Schatz H. Idiopathic macular holes. Am J Ophthalmol. 1985;99(4):437-444. Kim JW, Freeman WR, Azen SP, el-Haig W, Klein DJ, Bailey IL. Prospective randomized trial of vitrectomy or observation for stage 2 macular holes. Vitrectomy for macular hole Study Group. Am J Ophthalmol. 1996;121(6):605-614. Marcgherio AR and Raphaelian PV. Chapter 61: Macular Holes and Epiretinal Membranes. http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v6/v6c061.html Chew EY, Sperduto RD, Hiller R, et al: Clinical course of macular holes. Arch Ophthalmol 117:242, 1999 Ip M, Baker BJ et al. Anatomical Outcomes of Surgery for Idiopathic Macular Hole as Determined by Optical Coherence Tomography. Arch Ophthalmol, 2002. Volume 120: 29-35. Hikichi T, Ishiko S et al. Scanning Laser Ophthalmoscope Correlations With Biomicroscopic Findings and Foveal Function After Macular Hole Closure. Arch Ophthalmol. 2000;118:193-197. Caskey, Patrick . Treating DME with Fovea-Friendly Micropulse Laser Therapy. October 2013. http://bmctoday.net/retinatoday/2013/10/article.asp?f=treating-dme-with-fovea-friendly-micropulse-laser-therapy Photos: http://www.bleedingcool.com/forums/front-page-film-tv-video-news/65124-back-future-writer-bob-galewithdraws-endorsement-hoverboard.html, http://geektyrant.com/news/2012/3/26/american-reunion-directors-want-to-remakeback-to-the-future.html From the Past to the Future Hope you enjoyed the ride Thank you! Special thanks to Dr. Heller and Dr. Marcus Fundus Photos From the chart: AN ATYPICAL CHOROIDAL NEVUS. “Appears atrophic next to pigmented area. Lesion has elevated margins and overlies larger typical pigmented nevus that extends nasal. Pigment rim to pigment rim is 4DD Hx 4.5 DD V. Michael Meyer OD Optometry Resident Daytona Beach VA OPC January 26 2014 Central white area is 2.5DD v x 2DD H Variable pigment with few drusen. (-) SRF on exam, (-) Lipofuscin or exudate overlying. “ Presentation at CEE CC: Fundus Photos No ocular complaints. “I’ve been getting my eye checked about every six months.” PMx HTN and Hyperlipidemia OHx PCIOL CE, OU 2011. h/o metal FB OS ~20 yrs prior Syst Meds Lisinopril, Atorvastatin, MV Eye Meds None OD OS VA’s (sc) 20/30+ 20/25- Pupils PERRL (-) APD EOMS FROM FROM CVF FTFC FTFC MRx IOP +0.50-0.75x085 +0.25-0.50x090 20/20 20/20 15 16 Presentation at CEE (Cont.) SLE OD OS Tr Bleph LLL Tr Bleph C/S w/q w/q AC d/q 3+ VHA d/q 3+ VHA Iris F/I F/I Lens PCIOL clear PCIOL clear DFE OD OS Vitreous Syneresis Syneresis ONH 0.25 inrr 0.25 inrr A/V 2/3 2/3 Macula Mild ERM Mild ERM Periphery (-) HBT Large Lesion Autofluorescence and Red-Free FAF: shows granulated pattern of diffuse hyperfl c/w RPE hypertrophy and distress with central area hypofl c/w RPE dropout/destruction. Red-Free: hyper-reflective rim with no visible choroidal lesion. Cirrus OCT: 5-Line Raster Assessment and Plan A: Atypical Choroidal Nevus OS - Stable with original photo ~8 yrs ago - B-Scan 2011 documented lesion as flat - Asymptomatic P: Continue to Monitor q 12 months 2/2 stability x 8 years 5-Line HD Raster of lesion shows RPE disruption and hypertrophy with focal areas of subretinal fluid. Sensory retina intact. Fundus Photos (2006 – 2013) ‘06 DDx: Choroidal nevus ‘09 • CHRPE • Malignant Melanoma • RPE Hyperplasia • Metastatic Carcinoma • Sub-RPE Hemorrhage • Benign Lymphoid Tumor • Chorioretinal Scar • Extramacular Disciform Lesion • Choroidal Hemangiomas • Localized Choroidal Detachment with Hemorrhage • Subretinal Effusion ‘12 ‘13 (1) • Choroidal Osteoma • RPE Window Defect • Choroidal Neurofibroma • Retinoschisis with Hemorrhage • Peripheral Melanocytoma • Intraocular Foreign Body Granuloma • Acquired Retinal Hemangioma Image Post-Processing Choroidal Nevus • A choroidal nevus “represents an acquired focal accumulation of melanocytes within the choroid that is of normal form and function.” (1) • May be Amelanotic (rare). • Multiple Nevi occur with Neurofibromatosis (1) Credit: Ivana K Kim,et al. “Choroidal Nevus..” • Increase in incidence into the mid-30s where incidence levels plateau. • Pregnancy may trigger nevi growth • Most are asymptomatic but may cause sequelae relating to RPE and Bruch’s membrane disruption. • Macular nevi may lead to decreased acuity. • Generally less than 2.0mm in height and less than 6mm in diameter with indistinct margins. • Prevalence: • NIH study: Total: 2.1%. Whites 4.1%, AA 0.7%, Hispanics 1.2%, Chinese 0.4% (2) • Blue Mountain Eye Study: 6.5% prevalence (whites) (3) Credit: Ivana K Kim,et al. “Choroidal Nevus..” Credit: Ivana K Kim,et al. “Choroidal Nevus..” Choroidal Melanoma Nevi Can Grow without Transformation • Most common primary ocular tumor in adults. (1) 1/6 million/year. (4) Left: 16 yr old F. • Focal accumulation of atypical melanocytes. Pigmentation varies Right: 23 years later with growth closer to fovea. Absence of SRF and orange pigment. and lesion may be amelanotic (rare). • Can begin as a benign nevus and may not transform for decades. • Although 1 case report of an adenocarcinoma arising from CHRPE. (4) • If a circumscribed, typically elevated (usually >2mm) and take on a Credit: Mukai,Shizuo et al.“Diagnosis of Choroidal ..” Credit: Mashayekhi, Arman, et al. “Slow Enlargment…” mushroom like or “collar-button” nodular appearance as it breaks through Bruch’s membrane. (1) • Less common are “diffuse” melanomas that have minimal apical height but are spread out over a large with poorly defined borders. (1) • Other common findings (although not universal): (5) Left: 65 yr old F. Large nevus with drusen • Documented Growth, height or base diameter Right: 31 years later with growth. • Orange pigment: lipofuscin filled macrophages, generally accepted as sign of tumor growth Credit: Mashayekhi, Arman, et al. “Slow Enlargment…” Credit: Mukai,Shizuo et al.“Diagnosis of Choroidal ..” • Sub-retinal fluid (10) • Absence of drusen (COMS) • Metastasis Left: 39 yr old F. • Poor prognosis • Greater risk with larger melanomas Right: 17 years later with overall enlargement. • Ocular melanosis: Doubles the rate of metastasis (6) Credit: Mashayekhi, Arman, et al. “Slow Enlargment…” Credit: Mukai,Shizuo et al.“Diagnosis of Choroidal ..” Nevus to Malignancy Transformation Collaborative Ocular Melanoma Study (COMS) • Rates of Nevi Transformation • Medium Tumors • 1:8000 / yr (4) • 1:4300 / yr (3) • 1:8845 / yr in whites (7) By age 80, risk of transformation 0.78% with slight yearly increases after that. (4) Mortality Rt • 10 year 12 year 10 18 21 11 17 17 Enucleation Nevus to Melanoma transformation defined as “enlargement in basal dimension or thickness of at least 0.5.” (4) Factors predictive of growth: “TFSOM” (1995) then “TFSOMUHHD” (2006) Large Tumors “To Find Small Ocular Melanoma, Use Helpful Hints Daily” T: F: S: O: M: U: H: H: D: 5 year I-125 BrachyTx Shields’ et al. retrospective studies. (5 and 8) • 3.1 - 8mm(h) <16mm (bd) (11 and 12) Thickness >2mm Fluid (subretinal) Symptoms Orange pigment Margin touching disc Ultrasound Hollowness Halo absence Drusen absence >2mm (h) & >16mm (b) or >10mm (h) (11 and 13) Mortality Rt PERT Enucleation Small Tumors Nevus to Malignancy Transformation (9) Verified Melanoma Mortality 5 year 10 year 26 45 27 40 Verified Melanoma Mortality 1-3mm (h) 5-16mm (b) (14) Mortality Rt 5 year 8 year Observation 6 14.9 Observation 1 All-Cause Mortality Verified Melanoma Mortality “Diffuse” Small Choroidal Melanoma Study (15) “Diffuse” small melanomas thickness/base = <20% All have overlying orange pigment. Credit: Shields, Carol et al. “Choroidal Nevus..” Credit: Shields, Carol et al. “Choroidal Nevus..” Credit: Shields, Carol et al. “Diffuse vs Non..” Credit: Shields, Carol et al. “Diffuse vs Non..” Credit: Shields, Carol et al. “Diffuse vs Non..” Credit: Shields, Carol et al. “Diffuse vs Non..” Credit: Shields, Carol et al. “Choroidal Nevus..” Credit: Shields, Carol et al. “Choroidal Nevus..” Top: (A) Orange pigment and SRF. (B) Enlargement Top: (E) Melanocytoma with orange pigment and SRF. (F) Enlargement after 2 years Bottom: (C) CN with overlying RPE atrophy. (D) Growth in height and development of central nodule with retinal invasion Bottom: (G) Suspicious CN with no drusen (H) Stable for 14 years, 15th year showed marked enlargement with an RD. + metastasis. Death 3 yrs post-enucleation. Credit: Shields, Carol et al. “Diffuse vs Non..” Credit: Shields, Carol et al. “Diffuse vs Non..” Small Melanocytic Lesions Small Melanocytic Lesions Stable “indeterminate” lesion. 12 years on, 1.35 mm to 1.4 mm Credit: Lane, Anne Marie et al. “Mortality...” Credit: Lane, Anne Marie et al. “Mortality...” Flat to 2.0 mm in 2 years with SRF. Symptomatic Dx as melanoma Treated with proton irradiation Credit: Lane, Anne Marie et al. “Mortality...” Credit: Lane, Anne Marie et al. “Mortality...” 20 months after initial presentation, Tx’d with proton therapy but developed metastasis 11 yrs after Tx. Credit: Lane, Anne Marie et al. “Mortality...” Credit: Evangelos Gragoudas, MD knut Credit: Evangelos Gragoudas, MD knut “Indeterminate lesion.” Rapid growth in 1 year to choroidal melanoma. (16) Credit: Lane, Anne Marie et al. “Mortality...” Credit: Evangelos Gragoudas, MD knut Giant Nevi Study Small Melanocytic Lesions Credit: Evangelos Gragoudas, MD “Nevus or …” Credit: Evangelos Gragoudas, MD knut (17) Credit: Li, HK et al. “Giant Choroidal…..” Small choroidal melanoma. Height: 2.2mm. (16) “Indeterminate lesion.” Observation w/o Tx. Orange pigment. Height 1.1mm to 1.2 mm, with larger basal diameter after 7 years. (16) Credit: Li, HK et al. “Giant Choroidal…..” Credit: Evangelos Gragoudas, MD “Nevus or …” Small choroidal melanoma with overlying orange pigment. Height: 2.2mm. (16) Credit: Li, HK et al. “Giant Choroidal…..” Halo Nevi Study Small Melanocytic Lesions (18) “Indeterminate lesion.” Observation w/o Tx. Multiple overlying drusen. Height <1mm Unchanged 2 years later. (16) Credit: Shields, Carol J et al. “Halo Nevus..” Internal halo (7.3% of population) Credit: Evangelos Gragoudas, MD knut Credit: Shields, Carol J et al. “Halo Nevus..” Halo nevus with overlying drusen Credit: Shields, Carol J et al. “Halo Nevus..” Reverse halo nevus Credit: Evangelos Gragoudas, MD knut “Indeterminate lesion.” Observation w/o Tx. Multiple overlying drusen. Height 1.2 mm Unchanged 5 years later. (16) Credit: Shields, Carol J et al. “Halo Nevus..” Credit: Shields, Carol J et al. “Halo Nevus..” Credit: Shields, Carol J et al. “Halo Nevus..” Posterior Pole Halo nevus, after 1 year, and after Tx with plaque radiotherapy and thermotherapy. Credit: Evangelos Gragoudas, MD knut Credit: Evangelos Gragoudas, MD knut Evaluation: Autofluorescence Evaluation: Fundus Photos Off-Axis Fundus Photos (19) Nevi Normal eye. At right, camera slightly offaxis, producing a reddish crescent (arrows) at temp fovea edge. Distorts macula image but not surrounding BVs. Credit: Johnson, Robert et al. “Camera Artifacts...” Credit: Johnson, Robert et al. “Camera Artifacts...” Right image: Off-Axis Credit: Lavinsky, D et, al. “Fundus Autofl...” Credit: Johnson, Robert et al. “Camera Artifacts...” Credit: Lavinsky, D et, al. “Fundus Autofl...” Credit: Johnson, Robert et al. “Camera Artifacts...” Right image: Off-Axis Credit: Johnson, Robert et al. “Camera Artifacts...” Credit: Shields, Carol J et al. “Halo Nevus..” Credit: Johnson, Robert et al. “Camera Artifacts...” Credit: Shields, Carol J et al. “Halo Nevus..” Evaluation: Autofluorescence Evaluation: Fundus Photos Melanoma “Different Cameras, Different Colours.” (20) Small Choroidal melanoma. L: Panoret. R: Optos Credit: A Schalenbourg, et al. “Pitfalls in Colour..” Credit: A Schalenbourg, et al. “Pitfalls in Colour..” Melanoma Orange pigment FAF: patchy hyperfl areas correlating with orange pigment. Credit: Gunduz, Kaan et al. “Correlation…” Credit: Gunduz, Kaan et al. “Correlation…” Choroidal nevus. L: Panoret. R: Spectralis Multicolor Credit: A Schalenbourg, et al. “Pitfalls in Colour..” Credit: A Schalenbourg, et al. “Pitfalls in Colour..” Choroidal hemangioma. L: Panoret. R: Spectralis Multicolor Credit: A Schalenbourg, et al. “Pitfalls in Colour..” Melanoma Diffuse orange pigment FAF: diffuse hyperfl pattern with absence of normal FAF drop-out in between Credit: Gunduz, Kaan et al. “Correlation…” Evaluation: OCT Evaluation: Ultrasonography • Melanomas typically consist of tightly packed homogenous cells and show low to moderate reflectivity on ultrasound. • As can happen with a large nevus, choroidal hemangioma, metastatic lesion, CHRPE, and RPE hyperplasia (1) B-Scans performed primarily to measure melanoma height and to appreciate any extra-scleral extension of the tumor. Extension most commonly discovered with presence of echolucent areas within the sclera. (21) Credit: Gunduz, Kaan et al. “Correlation…” NEVUS Orange pigment (?) Drusen Patchy pattern of distinct areas of hyperfl between areas of normal autofl. Credit: Gunduz, Kaan et al. “Correlation…” Credit: A Schalenbourg, et al. “Pitfalls in Colour..” • With respect to the COMS study, Credit: Gunduz, Kaan et al. “Correlation…” Credit: Byrne, SF et al. “Consistency of…” Credit: Byrne, SF et al. “Consistency of…” Evaluation: OCT EDI (Enhanced Depth Imaging) Sources, cont. 32. Singh AD, Mokashi AA, Bena JF, Jacques R, Rundle PA, Rennie IG. Small choroidal melanocytic lesions: features predictive of growth. Ophthalmology. 2006 (22) 33. 34. 35. 36. 37. 38. 39. Credit: Spaide, Richard F “Enhanced Depth…” Credit: Spaide, Richard F “Enhanced Depth…” 40. 41. 42. 43. 44. 45. 46. 47. Credit: Shah, Sanket U et al. ”Enhanced Depth…” Credit: Shah, Sanket U et al. ”Enhanced Depth…” Pearls Thank You TFSOMUHHD Evaluation • Photos • Proper alignment / multiple shots • Image processing • OCT • “EDI” • Long Wavelength • Fundus Autofluorescence Observation Frequency (9) • Non-suspicious nevi: • Bi-annually initially to determine stability, then a yearly DFE. • Suspicious, Large, Indeterminate nevi, or those with 1 to 2 of “TFSOMUHHD:” • F/Up every 4 to 6 months • Nevi with 3 or more features of “TFSOMUHHD:” • Refer to an ocular oncologist Sources 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 48. Jun;113(6):1032-9. Epub 2006 May 2. PubMed PMID: 16650475. Font RL, Zimmerman LE, Armaly MF. The nature of the orange pigment over a choroidal melanoma. Histochemical and electron microscopical observations. Arch Ophthalmol. 1974 May;91(5):359-62. PubMed PMID: 4132409. Lavinsky D, Belfort RN, Navajas E, Torres V, Martins MC, Belfort R Jr. Fundus autofluorescence of choroidal nevus and melanoma. Br J Ophthalmol. 2007 Oct;91(10):1299302. Epub 2007 Apr 12. PubMed PMID: 17431017; PubMed Central PMCID: PMC2000998. Gündüz K, Pulido JS, Pulido JE, Link T. Correlation of fundus autofluorescence with fluorescein and indocyanine green angiography in choroidal melanocytic lesions. Retina. 2008 Oct;28(9):1257-64. doi: .1097/IAE.0b013e31817d5cdc. PubMed PMID: 18626422. Demirci H, Cullen A, Sundstrom JM. ENHANCED DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY OF CHOROIDAL METASTASIS. Retina. 2013 Dec 17. [Epub ahead of print] PubMed PMID: 24351445. Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol. 2008 Oct;146(4):496-500. doi: 10.1016/j.ajo 2008.05.032. Epub 2008 Jul 17. Erratum in: Am J Ophthalmol. 2009 Aug;148(2):325. Pozonni, Maria C [corrected to Pozzoni, Maria C]. PubMed PMID: 18639219. 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Mukai, Shizuo et al. “Diagnosis of Choroidal Melanoma.” Albert & Jackobeic’s Principles 7 Practice of Ophthalmology. Third Edition. Ed by Daniel M Albert, Joan W Miller, Dimitri T Azar, Barbara A Blodi, Janet E Cohan, Tracy Perkins. Chapter 350, 4875-4886, W.B. Saunders Company 2000, Elsevier 2008. Shields CL, Furuta M, Thangappan A, Nagori S, Mashayekhi A, Lally DR, Kelly CC, Rudich DS, Nagori AV, Wakade OA, Mehta S, Forte L, Long A, Dellacava EF, Kaplan Shields JA. Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes. Arch Ophthalmol. 2009 Aug;127(8):989-98. doi: 10.1001/archophthalmol. 2009.208. PubMed PMID: 19667335. Kujala E, Mäkitie T, Kivelä T. Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci. 2003 Nov;44(11):4651-9. PubMed PMID: 14578381. Hawkins BS; Collaborative Ocular Melanoma Study Groupre-enucleation radiation of large choroidal melanoma: IV. Ten-year mortality findings and prognostic factors. 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Camera artifacts producing the false impression of growth of choroidal melanocytic lesions. Am J Ophthalmol. 2003 May;135(5):711-3. PubMed PMID: 12719084. 20. Schalenbourg A, Zografos L. Pitfalls in colour photography of choroidal tumours. Eye (Lond). 2013 Feb;27(2):224-9. doi: 10.1038/eye.2012.267. Epub 2012 Dec 14. PubMed PMID: 23238442; PubMed Central PMCID: PMC3574260. 21. Byrne SF, Marsh MJ, Boldt HC, Green RL, Johnson RN, Wilson DJ. Consistency of observations from echograms made centrally in the Collaborative Ocular Melanoma Study COMS Report No. 13. Ophthalmic Epidemiol. 2002 Feb;9(1):11-27. 22. Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol. 2008 Oct;146(4):496-500. doi: 10.1016/j.ajo.2008.05.032. Epub 2008 Jul 17. Erratum in: Am J Ophthalmol. 2009 Aug;148(2):325. Pozonni, Maria C [corrected to Pozzoni, Maria C]. PubMed PMID: 18639219. 23. Khalil MK. Balloon cell malignant melanoma of the choroid: ultrastructural studies. Br J Ophthalmol. 1983 Sep;67(9):579-84. PubMed PMID: 6882713; PubMed Central PMCID: PMC1040133. 24. McGovern VJ. Spontaneous regression of melanoma. Pathology. 1975 Apr;7(2):91-9. PubMed PMID: 1153228. 25. Shields CL, Furuta M, Mashayekhi A, et al. Clinical spectrum of choroidal nevi based on age at presentation in 3422 consecutive eyes. Ophthalmology. 2008; 115(3):546-552. 26. BergmanW,WillemzeR,deGraaff-ReitsmaC,RuiterDJ.Analysisofmajorhis- tocompatibility antigens and the mononuclear cell infiltrate in halo nevi. J Invest Dermatol. 1985;85(1):25-29. 27. Musette PH, Bachelez H, Flageul B, et al. Immune-mediated destruction of mel- anocytes in halo nevi is associated with local expansion of limited number of T cell clones. J Immunol. 1999;162(3):1789-1794. 28. Shields CL, Furuta M, Berman EL, et al. Choroidal nevus frequency of transfor- mation into melanoma: analysis of 2514 consecutive cases. Arch Ophthalmol. 2009;127(8):981-987. 29. Rishi P, Shields CL, Khan MA, Patrick K, Shields JA. Headache or eye pain as the presenting feature of uveal melanoma. Ophthalmology. 2013 Sep;120(9):1946-7.e2. doi: 10.1016/j.ophtha.2013.06.015. PubMed PMID: 24001534. 30. Lane AM, Egan KM, Kim IK, Gragoudas ES. Mortality after diagnosis of small melanocytic lesions of the choroid. Arch Ophthalmol. 2010 Aug;128(8):996-1000. doi: 10.1001/archophthalmol.2010.166. PubMed PMID: 20696999. Wet AMD-the current antiVEGF treatments; which one is the best? Case Presentation POHx: Katey Shea OD Optometry Resident Daytona Beach VA OPC Surgery: + CE c PCIOL OU, s/p Lucentis injections OS (appx q3 months since 7/2009) Trauma: (-) Disease: AMD, DM type 2 s DR Vision loss: + metamorphopsia OS Lazy Eye: (-) Eye Meds: Preservision FOHx: + glaucoma- mother Case Presentation Case presentation January 2010 81 yo Female Initial presentation to local retinal specialist in Daytona Beach. Has ben regularly seen by an Ophthalmologist in WV. Would like to initiate comanagement as she will be in Florida a few of the winter months each year. Case Presentation Case Presentation Visual Acuity (Initial Presentation) CC: + metamorphopsia OS with occasional, longstanding floater; no complaints OD (-)flashes or pain OU HPI: Macular Degeneration: Dry OD, Wet AMD OS with h/o injections; DM type ll; HTN cc OD: 20/30-1 PHNI OS: 20/40+1 PHNI Pupils: ERRL, 4mm in dim light, 2+rxn, (-) APD Motilities: FROM, (-) pain or diplopia OU CVF: FTFC OU IOP: PMHx: HTN, DM type ll, Bradycardia, Breast Cancer, Hypercholesteremia GAT OD: 16 OS: 17 Case presentation Right Eye Left Eye Case Presentation Macula OCT Central thickness OD: 187 OS: 182 Amsler grid image from: http://jejunesplace.blogspot.com/2010/09/amsler-grids.html Case Presentation SLE Case Presentation LLL: dermatochalasis OU C/S: nasal pterygium OU K: clear OU AC: d & q OU I: flat, (-) rubeosis OU Lens: PCIOL OU, mild PCO OS A/P 1. Dry AMD OD, Wet OS 2. DM s DR OU 3. Pseudophakia OU Case Presentation DFE Vitreous: syneresis OU C/D: 0.4 r OU A/V: 2/3 OU Macula: RPE changes OS>OD, no active CNV or DR OU Periphery: (-) holes, tears, detachments or hemes OU No active leakage today, OCT stable. Continue with HAG & Preservision. No injection today, last injection was 12/2009 (1 month ago) RTC 1 month f/u Continue tight glycemic control Monitor Case Presentation **Jump forward 2 years** Pt continued to have q1 month f/u care co-management with Retinal Specialist in Florida and West Virginia. Received Lucentis injections appx q2-3 months when deemed appropriate. Case Presentation March 2011 CC: s/p 3 month Lucentis OS. Still sees a dark spot centrally OS, unchanged. Pertinent findings: Pertinent Findings cont… DFE: RPE changes OS>OD, (-) DR, (-) CNV OU OCT: CT OD 178; OS 226 DFE: RPE changes OS>OD, small area of CNV parafoveal OS, AV nicking OU, (-) hemes OD OCT: OD 177; OS 219 Tx: Lucentis injection OS. RTC 1 month Case Presentation Note faxed from W. VA Ophthalmologist December 2012 A/P: TX: Lucentis injection given today OS, f/u 6-8 weeks in W. VA February 2012 CC: AMD f/u. No changes in VA for last 9 months. Lucentis q2 months. Last injection 12/2011 Pertinent findings: Macula surface taking on a rough appearance, with reduced foveal depression OS. Case Presentation VA: 20/30-1 OD, 20/200 with ecc gaze OS Amsler grid: OD normal; OS Hazy spot central Case Presentation Case Presentation Case Presentation January 2013 CC: Vision is stable OU, “no better or worse”. s/p Eylea injection 1 mo OD, 2 mo OS Pertinent findings: Pertinent findings: OD: FA show CNV, occult, late distinct leak much more than from a few microaneurysms. Eylea 4/2012, 5/2012, 6/2012, last on 10/2012, repeat Eylea injection today. OS: Poor but stable vision. Eylea 5/2012, 7/2012 and for recurrent leak 9/2012 and 11/2012. OCT today improved: observe. VA: OD 20/50+2 PHNI; OS 20/200 c ecc gaze PHNI. VA: OD 20/40 PHNI; OS 20/200 ecc gaze PHNI DFE: RPE changes c pigment clumps OD, Dry central scar OS, (-) active CNV OU, (-) DR OU OCT: OD 189/ OS 198 Tx: none indicated, RTC 1 mo f/u Case Presentation February 2013 CC: pt feels that she is straining more. Pt thinks RLL has a stye x 1.5 weeks. Pertinent Findings: VA: OD 20/50-2 PH 20/30+2; OS 20/200 ev DFE: no changes, (-) CNV, stable OCT: OD 218/OS 161 TX: Eylea maintenance injection OD, Monitor OSno tx indicated at this time. F/U in W. VA in 1 month Risk Factors for developing Macular Degeneration (6,7) Age ARM (Age-related maculopathy) + Family History Smoking Obesity Systemic vascular conditions – namely HTN Current Treatments & Recommendations Wet AMD Dry AMD Smoking cessation AREDS vitamin and mineral supplements Healthy lifestyle Observation Anti-VEGF Injections Avastin Lucentis Eylea Macugen PDT Thermal Laser Photocoagulation wAMD Studies of intravitreal anti-VEGF injection treatments CATT IVAN VIEW PIER EXCITE SUSTAIN SAILOR Image from: http://www.visivite.com/dry-maculardegeneration.html Risk factors for progression from Dry to Wet AMD(6,7) Bilateral drusen Multiple or confluent soft drusen Focal RPE hyperpigmentation Increased age over 75 Systemic vascular conditions: HTN, Hyperlipidemia, and DM Studies on Lucentis PIER EXCITE SUSTAIN SAILOR Image from: http://www.cnib.ca/en/your-eyes/eyeconditions/amd/the-eye/wet/Pages/default.aspx Image from: http://www.westtexasretina.com/site/lucentis.htm PIER(1,2) EXCITE(1) 24 month study 184 patient’s with subfoveal CNVM secondary to AMD Randomized 1:1:1 to Lucentis 0.3mg or 0.5mg or sham for 3 months (loading dose) followed by quarterly dosing. 12 month, randomized, double masked, non-inferiority study 353 patients with primary or recurrent subfoveal CNVM due to AMD Randomized 1:1:1 to receive monthly or quarterly Lucentis 0.3mg or quarterly Lucentis 0.5mg for 9 months after three initial monthly loading doses Image from: http://www.snoron.com/view-river_pier_at_sunsetwide.html PIER(1,2) Outcomes: At month 12 patients receiving quarterly Lucentis 0.5mg experienced a loss of -0.2 ETDRS letters from baseline After month 12 all sham group patients were switched to quarterly Lucentis 0.5mg. Sometime later in the 2nd year ALL patients were switched to 0.5mg MONTHLY dosing After four monthly injections patients gained 4.1 ETDRS letters BCVA scores had declined by -2.3 letters relative to baseline in the 0.5mg group (despite improvements after switching to monthly injections) PIER(1,2) Implications: Reducing Lucentis injection frequency to a quarterly basis led to losses in BCVA gains achieved during the loading phase Some restoration in visual acuity was observed after switching back to monthly doses during year 2 Monthly dosing or dosing that occurs more frequently than on a quarterly basis appears to provide the best benefit of Lucentis to patients EXCITE(1) Primary outcome measure= mean change in BCVA from baseline to month 12, with a non-inferiority limit of 6.8 ETDRS letters. Quarterly Lucentis 0.5mg FAILED to demonstrate non-inferiority to monthly Lucentis 0.3mg EXCITE(1) Secondary outcome measures= include mean change from baseline in CRT and proportion of patients with a gain/loss of ≥15 letters The proportion of patients with stable vision (< 15 letters lost) relative to baseline was similar A greater proportion of patients in the monthly treatment arm gained ≥15 letters at month 12 Mean decrease in CRT versus baseline was similar during the loading phase and at month 12 Participants randomized to quarterly dosing showed retinal thickening between scheduled injections while patients receiving monthly treatment experienced sustained improvements in retinal thickness EXCITE(1) Implications: SUSTAIN(1) Quarterly dosing with the licensed dosing (0.5mg) was not found to be equivalent to monthly dosing with a lower dose (0.3mg) OCT measures also favored monthly dosing Implications: SUSTAIN(1) 12 month open label, multicenter study 513 patients Lucentis was administered PRN following three monthly loading doses. Functional and anatomical improvements with Lucentis were greatest during the loading phase when treatment was administered monthly (3 months) Declines in both disease measurements were seen after the transition from monthly to PRN dosing SAILOR(1) 0.3mg Lucentis was used until 0.5mg Lucentis was approved, then all patients were switched to that Participants were assessed monthly and retreated if they lost > 5 ETDRS letters or gained >100 µm in CRT 12 month study, randomized cohort 2378 wAMD patients Administered Lucentis 0.3mg or Lucentis 0.5mg monthly for three months (loading phase) then treated PRN Retreatment criteria included loss of >ETDRS letters relative to the highest score at any previous visit or >100µm in CRT relative to the lowest value at any previous visit Retreatment assessments were performed on a quarterly basis Image from: http://thefilmstage.com/news/upcoming-popeye-animatedfeature-film-has-to-be-ultra-cartoony-to-work-says-director-genndytartakovsky/ SUSTAIN(1) Outcomes: BCVA scores in SUSTAIN increased during the loading phase, but decreased after the transition to PRNN dosing At study end patients gained 3.6 letters from baseline Greater decrease in CRT during the loading phase and slight increase and ultimate stabilization during the maintenance phase SAILOR(1) Outcomes: Lucentis 0.5mg Patients experienced a mean BCVA of 5.8-8.0 ETDRS letters, but that declined to a mean letter gain of 2.3 at month 12 Lucentis 0.3mg Patients experienced a mean letter gain of 1.7 at month 12 VIEW (VEGF Trap-Eye: Investigation of Efficacy and Safety in wAMD) (1,2) SAILOR(1) Implications: 2 randomized, multicenter, double masked, active controlled studies of Eylea in wAMD patients VIEW-1 was conducted in the USA and Canada VIEW-2 was conducted in Europe, Asia Pacific and Latin America Patients exhibited improvements in functional and anatomical disease measures with monthly Lucentis, which declined to some extent during the PRN treatment phase. Not much difference in BCVA between 0.3mg and 0.5mg dosing (1.7 letters vs 2.3 letters Quarterly follow up was too infrequent. Designs of the 2 studies were identical Studies on Avastin VIEW(1,2) None to date with research focused only on Avastin CATT (Head to head study of Avastin compared to Lucentis) Patients were randomized 1:1:1:1 to: Eylea 2mg q4 weeks Eylea 0.5mg q4 weeks Eylea 2mg q8 weeks with a sham injection every other month to preserve masking, or Lucentis 0.5mg q4 weeks Image from: http://www.nytimes.com/2011/08/31/health/31drug.html?_r=0 Studies on Eylea(1,2) VIEW (Head to head comparison of Lucentis and Eylea) VIEW(1,2) Outcomes: Eylea 2mg q8 was non-inferior to Lucentis 0.5mg for the primary endpoint Primary endpoint= stable vision at week 52 (<15 ETDRS letters lost) VIEW(1,2) CATT(1,2) Implications: Outcome at week 52: Visual and OCT outcomes for Eylea 2mg q8 were non-inferior to Lucentis 0.5mg q4 Using Eylea q8 may cause the same positive changes in the disease process that Lucentis 0.5 q4 with a reduced injection frequency. Avg # injections during study Eylea 7.6 Lucentis 12.3 VA with Lucentis q4weeks was non-inferior to PRN dosing. Comparison of Avastin with the two dosing schedules was inconclusive. The proportion of patients with stable vision and visual improvement did not differ between the two groups. The mean decrease in central retinal thickness (CRT), the proportion of patients without fluid on OCT and the proportion of patients without dye leakage on fluorescein angiography were greatest for Lucentis q4 weeks dosing. Image from: http://animalzfun.blogspot.com/2013/01/Animals-With-Glasses.html Head to head studies Avastin compared to Lucentis CATT(1,2) Outcomes CATT IVAN Eylea compared to Lucentis VIEW (previously mentioned) Image from: http://animalzfun.blogspot.com/2013/11/Funny-Animals-Glasses.html Image from:http://www.turnagaintimes.com/current%20issue/2011-11-17/head-tohead-combat.html CATT (1,2) 104 week multicenter, single masked, noninferiority trial 1208 wAMD patients Randomized to receive intravitreal injections of Lucentis 0.5mg or Avastin 1.25mg administered every 4 weeks or PRN with evaluations every 4 weeks. at week 104: VA differences favored q4 dosing vs PRN for both groups (Avastin and Lucentis) Lucentis q4 yielded the highest percentage proportion of patients without fluid on OCT In comparison to the patients who received q4 dosing for 2 years, the patients who were switched from q4 to PRN dosing (at the 52 week mark) experienced a larger mean decrease in vision during year 2 CATT(1,2) Implications: More frequent treatment schedules of both Avastin and Lucentis is needed to maximize long term outcomes of both VA and lack of fluid seen on OCT. q4 weeks > PRN dosing for both Avastin was equivalent to Lucentis for treatment of wAMD through 2 years with similar dosing schedules Image from: http://weheartit.com/entry/13091056 Image from: http://www.topdreamer.com/22-photos-cute-cats-with-sunglasses/ IVAN (Inhibit VEGF in Age Related Choroidal Neovascularization) (1,2) 24 month multicenter, non-inferiority factorial trial 610 patients with wAMD Randomized 1:1:1:1 to receive Lucentis 0.5mg or Avastin 1.25mg monthly for three initial doses (loading) followed by either monthly injections or PRN treatment with monthly f/u’s. Continuous treatment (q1month) vs discontinuous (PRN) IVAN(1,2) Outcomes: BCVA outcomes for Lucentis and Avastin for the continuous and discontinuous treatment were similar Fewer patients receiving the continuous treatment had fluid seen on OCT Comparison of Avastin with Lucentis, including both treatment regimens was inconclusive. IVAN(1,2) Implications: Results showed no difference in visual outcomes between dosing regimens and Avastin was not inferior to Lucentis OCT outcomes favored monthly administration compared to the PRN treatment arm Studies Summary(1,2) Most of the studies were in favor of treatment monthly or more frequently than quarterly (q3 months). PRN treatment should have follow ups more frequently than quarterly Quarterly treatment with Lucentis 0.5mg did not demonstrate non-inferiority to monthly treatments with Lucentis 0.3mg Eylea 2mg q8 weeks was non-inferior to Lucentis 0.5mg q4 weeks. Reviewing the most common anti-VEGF intravitreal injections Lucentis Avastin Eylea Image from: http://maculacenter.com/eye-procedures/avastin/ Lucentis (Ranibizumab) (1,2,4) Genentech FDA approved dosage 0.5mg/injection 2006 No set treatment schedule for wAMD but most studies indicate that monthly injections provide the best benefit Image from: http://preparing2qualify.com/wp-content/uploads/2013/02/dollar-sign.jpg Avastin (Bevacizumab) (1,2,4,5) Newest Kid on the Block(1,2,3,8) Genentech “Off-Label” use since 2005 Initially developed for the treatment of solid tumors and FDA approved in 2004 for treatment of metastatic colorectal cancer. Dosing is 1.25mg/injection Avastin vs Lucentis (2,6,9) Sorting through the options…(4) MOA: anti VEGF-A inhibitors Eylea (Aflibercept) Lexicomp FDA approval 2013 MOA: recombinant fusion protein that acts as a decoy receptor for VEGF-A, VEGF-B and PIGF Pricing is similar or slightly less than Lucentis Dosing for wAMD: intravitreal injection 2mg q4 weeks for 3 months then q8 weeks thereafter Is there a “first line treatment”? Lucentis is a smaller antibody fragment Preferred practice pattern guideline Market share/clinical use: Avastin>>Lucentis Cost What’s the biggest difference?? # injections Summary (1,2,7,9) Studies suggest the Eylea q8 weeks (after 3 monthly injections/ loading dose) is equivalent to Lucentis q4 week dosing. There is no “cook book recipe” to follow for treating wAMD Each Retinal Specialist/Ophthalmologist will have their own formula for treating wAMD and it will be tailored to each patient on a case by case scenario. Special Thanks to Dr. William Dunn & Staff Retinal Specialist Florida Retina Institute Daytona Beach, FL Daytona Beach VA Clinic Sources 1. Lanzetta P, Mitchell P, Wolf S, et al. Br J Ophthalmol Published Online First: [8 Aug 2013]. Doi:10.1136/bjophthalmology-2013-303394. (Accessed 5 Nov 2013). 2. Arroyo J. Age-related macular degeneration: Treatment and prevention. UpToDate. www.uptodate.com (Accessed 5 Nov 2013) 3. Aflibercept (ophthalmic): Drug information Lexicomp, Inc. UpToDate. www.uptodate.com (accessed 5 Nov 2013). 4. Age-Related Macular Degeneration Summary Benchmarks for Preferred Practice Pattern Guidelines. American Academy of Ophthalmology. October 2013. www.aoa.org. (accessed 5 Nov 2013) 5. Grisanti S and Ziemssen F. Bevacizumab: Off-label use in ophthalmology. Indiana J Ophthalmology. 2007 Nov-Dec; 55(6): 417-420 6. Kanski, Jack J. Clinical Ophthalmology: A systemic approach. 6th Ed. Edinburgh: Butterworth-Heinemann/Elsevier, 2007. Pgs 629-634 7. Alexander, Larry J. Primary Care of the Posterior Segment. Third Ed. McGraw-Hill, 2002. Pgs 92-108 8. Stewart MW. Expert Rev Clin Pharmacol. 2013 Mar;6(2):103-13. doi: 10.1586/ecp.12.81 http://www.ncbi.nlm.nih.gov/pubmed/23473589. (accessed 23 Dec 2013) 9. Avastin and Lucentis are equivalent in treating age-related Macular Degeneration. National Institute of Health. http://www.nih.gov/news/health/apr2012/nei-30a.htm (accessed 26 Dec 2013). Chief Complaint COLOSSAL CORNUNDRUMS • • • • 47 year old white male c/o FBS OS “I think something got in my eye last night” OHx: SCL wearer MHx: unremarkable Lee Guo, O.D. Chief Complaint (continued) Preliminary Testing • “I took my contacts out and flushed it, but this morning everything feels worse…” • “OMG… DO I HAVE PINK EYE???” • Visual Acuity • • • • • • • • (+) ocular pain / irritation (+) light sensitivity (+) thick white discharge (+) red eye – OD: 20/30 PH 20/20 – OS: 20/30-2 PH NI Pupils: ERRL (-)APD OD, OS EOMs: FROM OU CFs: FTFC OD, OS CT: ortho • SLE Clinical Findings – L/L: mild LUL erythema, mod lash crusting OU – CONJ: OD: white and quiet OS: 3+ injection and mild chemosis – K: OD: clear to NaFl OS: temp: 4.0mm crescent epi defect overlying 5.5 x 4.5 SEI nas: 1.5h/2.0v mm epi defect overlying 3.0mm SEI sub epi haze/edema, mild central descemet folds, ropy mucopurulent discharge – AC: deep and quiet OD, 4+ cells & tr flare OS – Iris: flat and intact OU Questions Diagnosis What would cause this odd presentation? - Infranasal and temporal ulceration - 4+ cellular AC reaction Atypical Corneal Ulcerations OS - likely contact lens related - poor I/R technique? Infected abrasion? - CL abuse (sleeps/showers/swims in CLs) What are your differentials? What is your treatment approach? Treatment • Vigamox loading dose then Qhr • Voltaren QID • Bacitracin + Polymyxin B ung QHS DAY 2 • CC: “Umm I used the meds doc, but I feel worse and now I can’t see.” • Visual Acuity – OD: 20/30 PH 20/20 – OS: 20/200 PH 20/100 • Dx Refraction: OD: -1.50 -1.00 x120 OS: NIWL 20/20 20/200 DAY 2 (continued) • Tonometry: 15, 10 • SLE (OS) – CORNEA • 3.0v/2.5h mm yellow elev ulcer inf-nas • 3.5v/3.0h mm yellow elev ulcer temp overlying 4.5v/5.5h mm confluent infiltrate with 3 wispy extensions sup-nas, inf-nas, inf-temp • Cobbweb-like endothelial thinning vs breaks central • 2+ descemet folds – AC : 4+ cell w/plasmoid flare, (+)hypopyon DAY 2 (continued) DAY 2 - Questions WHAT HAPPENED??? Revisit OHx… • “Sooo I got my contacts as samples from Lenscrafters? They didn’t tell me I couldn’t swim in them… I use my jacuzzi every night and only slept in them for one week…” In light of new history, what’s now on your list of differentials? Any additional testing? Any changes to your treatment? DAY 2 (continued) NEW TREATMENT • Fortified VANCOMYCIN 25mg/ml + Fortified TOBRAMYCIN 15mg/ml – alternating every 1/2 hour for first 6 hrs then alternating every hour around the clock9 • Cyclopentolate BID • *Tobradex BID – *added per recommendation by corneal specialist after first 6 hrs loading dose of fortifieds completed FORTIFIED Tx PEARLS 1. NO SLEEP. Make it clear to pt: you’re in for a restless night - round the clock dosing 2. EXPIRATION. Fortified meds made at compounding pharmacy, tobra lasting 1 week, vanco lasting 2 weeks – may need to order more 3. REFRIGERATION. For better compliance, have one drop in fridge, other on deck near pt alternate bottle locations Q30min for less confusion DAY 3 • CC: “Well. I feel better. Still can’t see.” • Visual Acuity (unchanged): – OD: 20/30 PH 20/20 – OS: 20/200 PH NI • Dx Refraction (unchanged): OD: -1.50 -1.00 x120 OS: NIWL 20/20 20/200 DAY 3 (continued) • Tonometry: 16, 08 • SLE (OS) • • • • Ulcer sizes unchanged but borders less defined Wispy extensions now pockets of neg staining Descemet folds, AC rxn, & hypopyon unchanged No signs of perforation • Fortified dosing change – alternating every hour until midnight then alternating every 2 hours DAY 4 • CC: “I feel better. Vision feels the same.” • Visual Acuity: – OD: 20/30 PH 20/20 – OS: 20/400 PH NI • Dx Refraction (unchanged): OD: -1.50 -1.00 x120 OS: NIWL 20/20 20/400 DAY 4 (continued) • Tonometry: 14, 08 • SLE (OS) • • • • Nasal ulcer decreased, temp infiltrate decreased Marked incr k edema (cause of decr vision) mild AC rxn to view, hypopyon unchanged No signs of perforation • Fortified dosing change – alt Q2h until 10pm, Q3h until 4am, then Q4h – Increase Tobradex to TID Summary of Day 5-10 (cont) • Fortified dosing changes : – Day 5: alt Q4h x 12h then Q6h x 12 h • Increase Tobradex to QID • Start celluvisc Qhr, lacrilube Qhr – Day 6: alt Q6h x 18h then Q8h • Switch Tobradex to Pred Forte QID – Day 7-10: alt Q8h x 24h Summary of Day 5-10 • Visual Acuity: BCVA eventually incr to 20/100 to 20/80 as k edema slowly decreased • Tonometry: no acute hypotony nor OcHTN • SLE (OS) • Ulcers and infiltrate sizes slowly decr • K edema relatively stable but descemet folds decr • Hypopyon disappeared on day 5 Summary of Day 11-22 • Visual Acuity: BCVA eventually incr 20/40- on Day 11 and slowly to 20/20-2 by Day 18 • Tonometry: no acute hypotony nor OcHTN • SLE (OS) • Ulcers and infiltrate sizes slowly decr with residual stromal scarring and thinning central to each ulcer • K edema slowly resolved Summary of Day 11-22 (cont) • Fortified dosing changes : – Day 11-18: alt Q12h x 24h • aka fort vanco QD, fort tobra QD – Day 19-22: d/c fortified, start PF taper • Continue celluvisc + lacrilube long term Discussion • Fortunate full visual recovery, residual scarring, no perforation • Microorganism responsible unknown, but etiology clearly contact lens abuse • Culture not performed … but it should be • Possible for k ulcers to worsen / plateau • Initial presentation + OHx suspect for fungal and acanthamoeba • Double ulcer pattern likely 2’ to poor I/R technique, infected k abrasion where CL was being “pinched off” during removal Differential Diagnosis • • • • • • • • Bacterial • K abrasion Fungal • RCE Acathamoeba • Neurotrophic HSV & HZV • Topical anesthetics Atypical mycobacteria abuse Sterile ulcer / infiltrate • Foreign body / rust ring Staph hypersensitivity Autoimmune (RA, Sjogrens) Vision Threatening Corneal Ulcers Tx Approach • Always co-manage with corneal specialist • Photos, fortified antibiotics, cyclo, culture – modify Tx immediately per culture results • NO CONTACT LENS WEAR!!! • IOP – monitor / Tx uveitic glaucoma, no prostaglandins • Pain meds – review all contraindications pregnancy, bleeding disorders, stomach ulcers & other GI disorders, renal/liver disease Vision Threatening Corneal Ulcers Tx Approach (continued) • OTHER CONSIDERATIONS: – Eye shield (NOT PATCH) for k thinning – Doxy 100 mg bid – antimetalloproteinase suppresses connective tissue breakdown to prevent perforation – Hospital Admission for oral fluoroquinolones and other systemic antibiotics IF: • Tx plateau / markedly worsening ulceration • Suspect poor patient compliance • Impending perforation Vision Threatening Corneal Ulcers Tx Approach (continued) • Once infection under control… – heavily lubricate w/ NP tears – consider topical corticosteroid for k edema HOWEVER, carefully monitor : will worsen significantly w/ aggressive fungi, mycobacteria, pseudomonas • Repeated ulcer measurements + pachymetry to monitor resolution and k edema New Treatments • Collagen cross-linking • Amniotic Membrane + serum tears • IF PERFORATION … refer for corneal transplant Corneal Collagen Cross-linking Collagen cross-linking for resistant corneal ulcer (2013)1 • 10 infectious k pts – unresponsive to fortified antibiotics • Cultures: staph aureus, epidermidis, aspergillis • 8/10 healed + scar (4/8 c 20/20 VA) Riboflavin/ultravoilet light-mediated crosslinking for fungal keratitis (2013)2 • 8 fungal keratitis pts – cultures: fusarium, aspergillus • All cases healed epithelium within 8 days Corneal Collagen Cross-linking (continued) Conclusion • CXL may be future Tx for resistant infectious keratitis3, esp w/ ↑antibiotic resistance • current literature shows CXL holds promise Tx for infectious keratitis HOWEVER: larger-scale, randomized, controlled trials comparing cross-linking to standard antibiotic therapy still warranted 4 Amniotic Membrane + Serum Tears Amniotic Membrane + Serum Tears (continued) Amniotic membrane transplantation for acute Pseudomonas keratitis (2012)5 • 14 eyes Tx AMT, 11 eyes Tx antibiotics (control) Conclusion • AMT results: immed pain relief, ↓density final k opacity, and better VA at the final follow-up • Amniotic membrane transplantation (AMT) effective Sx option for k ulcerations, both infectious5 and non-infectious7,8 Effectiveness of topical autologous serum treatment in neurotrophic keratopathy (2013)6 • 19 pts w/neutrotrophic k at 20% autologous topical serum • 91% epi healing within 12 weeks • 71% improved BCVA • Autologous serum eye drops effective supplementary therapy8 or primary Tx for noninfectious ulcerations6 (i.e. neurotrophic) Final Thoughts • For ALL contact lens wearers: EDUCATE EDUCATE EDUCATE • As our pt demonstrates, results of CL abuse can be catastrophic • Even established wearers still rinse cases w/ tap water and shower in CLs • In terms of compliance: daily > monthly > 2 week > extended • When in doubt, refer it out QUESTIONS? References THANK YOU 1. Sorkhabi R, Sedgipoor M, Mahdavifard A (2013). “Collagen crosslinking for resistant corneal ulcer.” Int Ophthalmol. 2013 Feb;33(1):61-6. doi: 10.1007/s10792-012-9633-2. Epub 2012 Sep 27. 2. Li Z, Jhanji V, Tao X, Yu H, Chen W, Mu G (2013). “Riboflavin/ultravoilet light-mediated crosslinking for fungal keratitis.” Br J Ophthalmol. 2013 May;97(5):669-71. doi: 10.1136/bjophthalmol-2012-302518. Epub 2013 Jan 26. 3. Sağlk A, Uçakhan OO, Kanpolat A (2013). “Ultraviolet a and riboflavin therapy as an adjunct in corneal ulcer refractory to medical treatment.” Eye Contact Lens. 2013 Nov;39(6):413-5. doi: 10.1097/ICL.0b013e3182960fdf. 4. Tayapad JB, Viguilla AQ, Reyes JM (2013). “Collagen cross-linking and corneal infections.” Curr Opin Ophthalmol. 2013 Jul;24(4):288-90. doi: 10.1097/ICU.0b013e32836229c5. References (continued) 5. Kheirkhah A, Tabatabaei A, Zavareh MK, Khodabandeh A, Mohammadpour M, Raju VK (2012). “A controlled study of amniotic membrane transplantation for acute Pseudomonas keratitis.” Can J Ophthalmol. 2012 Jun;47(3):305-11. doi: 10.1016/j.jcjo.2012.03.014. 6. Guadilla AM, Balado P, Baeza A, Merino M (2013). “Effectiveness of topical autologous serum treatment in neurotrophic keratopathy.” Arch Soc Esp Oftalmol. 2013 Aug;88(8):302-6. doi: 10.1016/j.oftal.2012.09.033. Epub 2013 Jan 18. 7. Chen HJ, Pires RT, Tseng SC (2000). “Amniotic membrane transplantation for severe neurotrophic corneal ulcers.” Br J Ophthalmol. 2000 Aug;84(8):826-33. 8. Lavaju P, Sharma M, Sharma A, Chettri S (2013) “Use of amniotic membrane and autologous serum eye drops in Mooren's ulcer.” Nepal J Ophthalmol. 2013 Jan;5(9):120-3. 9. The Wills Eye Manual 5th Edition (2008). Chapter 4 Cornea
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