Adventures in Posterior Segment Grand Rounds 46 W F. 46 W F central blindness. The not so fine print.

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1 Adventures in Posterior Segment Grand Rounds The not so fine print. All views in this talk, including off-label (non-usa-fda approved) use of medications, are solely those of the presenter Leo Semes, OD Professor, UAB Optometry The presenter has served as consultant for, and/or received research support and/or speaking honoraria from and/or is an advisory board member Alcon, Allergan, Merck, Novartis, Pharmacia/Pfizer, Carl Zeiss Meditec, OptoVue, MedOP, and SightPath Medical 2 46 W F C/O central blindness both eyes (09/05) Released from hospital Acute pancreatitis Dyslipidemia Uncontrolled systemic hypertension Suspected to be 2 0 to alcohol abuse 46 W F central blindness BSCVA: 20/25(OD) 20/30 (OS) [EV] Pertinent lab results Triglycerides > 4000 CBC w/diff, ESR, CRP (WNL) Fundi showed cotton wool spots The optic discs are unaffected The foveal reflex is absent There is evidence of disruption at the level of the nerve fiber layer that is more evident in the right eye Red-free images of the right and left eyes enhances infarcts of the nerve fiber layer.

2 Right eye and Right VF Notice the deep central depression. Left eye Notice the deep central depression. FA study Red Free FA study No leakage at 47 sec Note: patchy choroidal filling FA study FA study No leakage from retinal or choroidal vessels at 1:03 and 3:21 Patchy choroidal filling still evident No late leakage in the right eye, either

46 WF with decreased central VA and abnormal choroidal filling Purtscher Retinopathy PubMed search: visual field defect, cotton wool spots Meyer CH, Callizo J, Schmidt JC, Mennel S.

3 46 WF with decreased central VA and abnormal choroidal filling Purtscher Retinopathy PubMed search: visual field defect, cotton wool spots Meyer CH, Callizo J, Schmidt JC, Mennel S. Functional and anatomical findings in acute Purtscher's retinopathy. Ophthalmologica. 2006;220(5): Purtscher Retinopathy Initially associated with head trauma and crush injuries Current thinking Micro circulatory defects secondary to endothelial cell damage (ischemic macula) 46 WF Purtscher Retinopathy W/in 3 weeks VA 20/20 (OD) and 20/25 (OS) Fundus picture improved Medications include: Diovan 160 mg. po qd (Valsartan and Hydrochlorothiazide ) for HBP Pravachol 40 mg po qd Zocor 80 mg po ad Librax 2 tab po qhs (Librium (chlordiazepoxide hydrochloride) + the anticholinergic/spasmolytic effects of Quarzan (clidinium bromide) Questions Comments Purtscher Retinopathy 61 B/M 12/02 Followed X 12 years - Angioid Streaks 2 0 A1 Hemoglobinopathy VA 20/40 61 B/M 12/02 Followed X 12 years - Angioid Streaks 2 0 A1 Hemoglobinopathy VA 20/25 (OS) note less involvement

Angioid Streaks - CNVM 61 B/M (11/03) compare FA and

symptomatic VA 20/30 (OD) note increased involvement RTC

Pt returns X 3 weeks C/O distorted VA (20/80) 11/03 compare

Free Early note Hyperfluorescence (leakage) Angioid Streaks

4 Angioid Streaks - CNVM 61 B/M (11/03) compare FA and clinical (X 3 weeks / VA = 20/80) 62 B/M (10/03) AS now symptomatic VA 20/30 (OD) note increased involvement RTC 4-5 mo. Pt returns X 3 weeks C/O distorted VA (20/80) 11/03 compare RF and clinical (3 weeks later) Angioid Streaks - CNVM Red Free Early note Hyperfluorescence (leakage) Angioid Streaks - CNVM Angioid Streaks - CNVM Midphase: Note leakage associated with AS and from CNVM Late phase leakage consistent with CNVM

Angioid Streaks - CNVM Angioid Streaks - CNVM 63 B/M (9/04) Late

significant clinical picture consistent with remodeling following

Lack of leakage Indicating stable macula 48 sec.

5 Angioid Streaks - CNVM Angioid Streaks - CNVM 63 B/M (9/04) Late phase leakage consistent with CNVM Verteporfin VA 20/80 (OD) note significant clinical picture consistent with remodeling following Verteporfin treatment 61 B/M (9/04) 31 sec RF Note poor perfusion Lack of leakage Indicating stable macula 48 sec. 9:56 sec Late-phase staining No leakage Note lack of leakage (stabilized CNVM) LS

63 W/M Questions Comments When I was grilling on July 4,

sparklers 07/ 24/ 2007 VA 20/20 in each eye Anterior

6 63 W/M Questions Comments When I was grilling on July 4, I noticed sparks and floaters in my left eye. I thought it was time for a CL check, so I came in to see you Sudden onset No other symptoms 63 W/M with sparklers 07/ 24/ 2007 VA 20/20 in each eye Anterior segment evaluation unremarkable for age DFE... (OS) 07/ 24/ /14/ 2007

7 Outcomes Let s back up...08/14/ 2007 Sent to Internist for evaluation Complained of dizziness to Internist Carotid Doppler performed Sufficient blockage to recommend carotid endarterectomy Done within 3 weeks of visit to UABSO Successful procedure 45 F Questions Comments VA = 20/20 Normal history Baseline photo 2000 Predisposing conditions to retinal vein obstruction? Sudden onset of reduced VA (X 7 ½ yrs) 20/80 w/central disturbance What are you going to do? 52 W F 52 W F 9/ 4/ 2008 Involvement confined to the inner retina

52 W F 52 W F 9/ 9/ 2008 Cystoid macular edema;

resolution 52 W F 1/ 19/ 2009 Continued on Xibrom

8 52 W F 52 W F 9/ 9/ 2008 Cystoid macular edema; Started on Xibrom (bromfenac) qid) 9/ 22/ 2008 VA 20/200; distinct macular involvement; Now what? 52 W F 1/ 14/ 2009 Continued on Xibrom qid Some resolution 52 W F 1/ 19/ 2009 Continued on Xibrom qid 52 W F 2/ 17/ 2009 Continued on Xibrom qid 52 W F

9 52 W F 52 W F Uninvolved OS 52 W F 52 W F 2/ 16/ 2009 Cystoid macular edema; Still on Xibrom (qid) 52 W F 2/ 16/ 2009 Recommend anti-vegf intravitreal injection VF 2/ 24/ 2009 But wait, there's more

10 VF 2/ 24/ 2009 And an Avastin injection Questions Comments VA = 20/25!!! Restoration of normal anatomy 86 YO 20/80 What s your diagnosis? Presents with reduced VA OS POH: repaired retinal hole SN OS X 11 yrs Pseudophakic in each eye Medicated for HTn X 20 yrs Retinal angiomatous proliferation Aka Type III neovascularization Management Avastin injection 3 weeks

11 28 W/M Questions Comments History / RFV Healthy Dental Student II 2-day observation of floater OD only No current medications/allergies No chronic or acute medical problems 28 W/M Findings UCVA 20/20 in each eye Normal motility VF - FFCF PERLA (-) APD Anterior segment unremarkable OD/OS TA 14/14 mm Hg (OD/OS) 28 W/M Findings (con t) DFE Vitritis (OD) Granuloma 28 W/M Note disc swelling What are some differential diagnoses? Toxoplasmosis Histoplasmosis Toxocariasis Cat-scratch neuroretinitis

12 28 W/M DFE (OD) Granuloma + Elevated nasal disc margin + parapapillary retinal edema = Neuroretinitis! Uninvolved Fellow eye 28 W/M Cat-scratch neuroretinitis optic disc (OD) Slight optic nerve head edema with spread to retina on nasal side (OD) History of new kittens with scratch (still healing) on back of left hand 28 W/M Treatment Bactrim DS 1 tab, PO, bid X 4 wks. 28 W/M Discussion Optic nerve swelling as an early sign in cat-scratch disease Wade NK, Levi L, Jones MR, et al. Optic disk edema associated with peripapillary serous retinal detachment: an early sign of systemic Bartonella henselae infection. Am J Ophthalmol 2000; 130:

Case Example 28 W/M Cat-scratch neuroretinitis

trimethoprim] bid X 2 weeks and re-check

attenuation, sclerosis, disc edema, pale retina,

13 Case Example 28 W/M Cat-scratch neuroretinitis Treatment with Bactrim DS [sulfmethoxazole + trimethoprim] bid X 2 weeks and re-check Serology to confirm diagnosis Resolution is sometimes spontaneous without ocular consequences S/P 2 days of Bactrim tx. Neuroretinitis with CRAO, CRVO, (& NVG) Neuroretinitis with CRAO, CRVO, & NVG Arterial attenuation, sclerosis, disc edema, pale retina, resolving macular 1 month Disc edema Dilated tortuous veins Thin arteries Intraretinal hemorrhages Retinal pallor 49 sec fails to reveal retinal perfusion Neuroretinitis (optic disc edema with macular star, ODEMS) ODEMS (May be bilateral) Note choroidal lesions on the RF photo

ODEMS: FA ODEMS: FA Early: Retinal arterioles filled;

Mid: Dilated disc vessels and hypofluorescence in choroid

http://www.southeasterneyecenter.com/cases/catscratch.

Desires second opinion on treatment for retinal problem

weeks (D/C) VA (OD) 20/200, mild vitritis, no A/C rxn.

appearance @ initial presentation Initial treatment 39 W/M

14 ODEMS: FA ODEMS: FA Early: Retinal arterioles filled; patchy choroidal filling Late: Patchy choroidal lesions Mid: Dilated disc vessels and hypofluorescence in choroid Mid phase ICG: many hypofluorescent choroidal lesions. Case: 39 W/M Questions Comments Initial presentation: Desires second opinion on treatment for retinal problem History: taking clindamycin X 6 weeks PO + steroids PO X 3 weeks (D/C) VA (OD) 20/200, mild vitritis, no A/C rxn., all else unremarkable; OS uninvolved 39 W/M OD Fundus initial presentation Initial treatment 39 W/M Bactrim DS (160 mg. Trimethoprim mg. Sulfmethoxizole) PO bid X 2 weeks RTC X 2 wks

39 W/M 2- week return visit (fundus appearance) 39 W/M VA unchanged Vitritis slightly diminished Fundus appearance essentially unchanged Options Continue meds??? Change meds??? Add meds??? Refer?

15 39 W/M 2- week return visit (fundus appearance) 39 W/M VA unchanged Vitritis slightly diminished Fundus appearance essentially unchanged Options Continue meds??? Change meds??? Add meds??? Refer??? 39 W/M 4-week return visit VA unchanged Vitritis resolved; 1+ A/C reaction Fundus appearance essentially unchanged Options Continue meds??? Change meds??? Add meds??? Refer??? 8-week return 39 W/M Patient C/O itch on shoulders and back VA 20/100 A/C reaction resolved Fundus remodeling apparent Now what??? Case: 39 W/M Fundus appearance at discharge visit Treatment indications 1 Involvement within the macular arcades Proximity of lesion to optic nerve Relative indications infection in immunocompromised patients marked vitreous reaction (posterior uveitis) active lesion in an only eye presentation in an elderly patient (shown to be more aggressive) 1. Stanford MR, Gilbert RE. Treating ocular toxoplasmosis: current evidence. Mem Inst Oswaldo Cruz. 2009;104(2):312-5.

Ocular toxoplasmosis presentations Ocular toxoplasmosis presentations Commodaro AG, Belfort

Mem Inst Oswaldo Cruz. 2009;104(2):345-50. Commodaro AG, Belfort Mem Inst Oswaldo Cruz.

16 Ocular toxoplasmosis presentations Ocular toxoplasmosis presentations Commodaro AG, Belfort RN, Rizzo LV, et al. Ocular toxoplasmosis: an update and review of the literature. Mem Inst Oswaldo Cruz. 2009;104(2): Commodaro AG, Belfort RN, Rizzo LV, et al. Ocular toxoplasmosis: an update and review of the literature. Mem Inst Oswaldo Cruz. 2009;104(2): Ocular toxoplasmosis presentations Ocular toxoplasmosis presentations Commodaro AG, Belfort RN, Rizzo LV, et al. Ocular toxoplasmosis: an update and review of the literature. Mem Inst Oswaldo Cruz. 2009;104(2): Commodaro AG, Belfort RN, Rizzo LV, et al. Ocular toxoplasmosis: an update and review of the literature. Mem Inst Oswaldo Cruz. 2009;104(2): Ocular toxoplasmosis presentations Ocular toxoplasmosis presentations Commodaro AG, Belfort RN, Rizzo LV, et al. Ocular toxoplasmosis: an update and review of the literature. Mem Inst Oswaldo Cruz. 2009;104(2): Commodaro AG, Belfort RN, Rizzo LV, et al. Ocular toxoplasmosis: an update and review of the literature. Mem Inst Oswaldo Cruz. 2009;104(2):

Additional features 1 OCT features of Toxoplasmic retinochoroiditis Punctate outer retinal toxoplasmosis Retinal vasculitis Retinal vascular occlusions Rhegmatogenous RD with serous RD Unilateral

heterochromic iridocyclitis Reflective inner retina in active presentations Posterior hyaloid thickened and detached over the lesion Shadowing of the underlying choroid May have serous fluid Monnet

17 Additional features 1 OCT features of Toxoplasmic retinochoroiditis Punctate outer retinal toxoplasmosis Retinal vasculitis Retinal vascular occlusions Rhegmatogenous RD with serous RD Unilateral pigmentary changes simulating RP Neuroretinitis and other forms of optic neuropathy Peripheral retinitis and scleritis In children: Cataract, CNV, glaucoma, RD Has been associated with Fuch s heterochromic iridocyclitis Reflective inner retina in active presentations Posterior hyaloid thickened and detached over the lesion Shadowing of the underlying choroid May have serous fluid Monnet D, Averous K, Delair E, Brézin AP. Optical coherence tomography in ocular toxoplasmosis. Int J Med Sci. 2009;6(3): Commodaro AG, Belfort RN, Rizzo LV, et al. Ocular toxoplasmosis: an update and review of the literature. Mem Inst Oswaldo Cruz. 2009;104(2): Management of Ocular Toxoplasmosis Clinical Presentation / Diagnosis Observation of a yellowish lesion with overlying inflammatory cells is almost diagnostic Vitritis/choroiditis may accompany Blood tests are definitive (systemic) but not in ocular Sabin-Feldman methylene blue dye test, IgG, IgM, ELISA) Treatment is indicated when the posterior pole is involved Ocular Toxoplasmosis 30% - 50% of all cases of posterior uveitis Clinical presentation (same for cong. and acq.) Focus of necrotizing retinitis Moderate to severe vitritis In immunocompromised patients, there may be multiple foci or extensive necrosis Ocular Toxoplasmosis Clinical epidemiology 1 billion infections worldwide More prevalent in tropical climates US seropositivity: 3-70% of adults Prevalence 6% Ratio: acq. 10X more common than cong Da-la-Torre A, et al. Screening by ophthalmoscopy for Toxoplasma retinochoroiditis in Columbia. Am J Ophthalmol 2007; 143: 354.] T. Gondii (multiple pathway risks) parasitic sexual lifecycle

18 Toxoplasmic Retinochoroiditis Toxoplasmosis gondii (obligate intracellular parasite (Cl: Sporoza)) T. gondii Parasitic sexual lifecycle Cat / undercooked meat as vectors Human infection accidental ingestion/inhalation of oocytes Transplacental transmission possible; may be fatal T. Gondii (multiple pathway risks) Toxoplasmic Retinochoroiditis Toxoplasmosis gondii (obligate intracellular parasite (Cl: Sporoza) Congenital toxo 70% asymptomatic 10% w/ophthalmic manifestations most will later develop ocular manifestations T. Gondii (multiple pathway risks) lifecycle Feline advisory board Management of Ocular Toxoplasmosis Treatment recommendations Vision decreased due to macular involvement Posterior pole or Optic nerve threat (geographically) Peripheral lesions (outside arcades) - Observation Management of Ocular Toxoplasmosis Treatment Options Classic Strategy (historical) Pyrimethamine - 75 mg loading dose followed by 25 mg daily for 1-2 weeks [must be supplemented with folinic acid] Triple sulfonamides - 2g loading dose followed by 1 g QID for 3 weeks

Management of Ocular Toxoplasmosis Treatment Options Alternatives (sulfa allergy) Clindamycin - 300 mg QID for 3 weeks + Oral prednisone - 60 to 80 mg every other day at breakfast; taper in 3-4 weeks

/ day X 5 weeks); SE associated anterior uveitis is managed with cycloplegics and 1% prednisolone acetate Management of Ocular Toxoplasmosis Treatment Option of Choice (TOC) Bactrim DS (160 mg

19 Management of Ocular Toxoplasmosis Treatment Options Alternatives (sulfa allergy) Clindamycin mg QID for 3 weeks + Oral prednisone - 60 to 80 mg every other day at breakfast; taper in 3-4 weeks Azithromycin (500 mg. Loading dose; 250 mg. / day X 5 weeks); SE associated anterior uveitis is managed with cycloplegics and 1% prednisolone acetate Management of Ocular Toxoplasmosis Treatment Option of Choice (TOC) Bactrim DS (160 mg trimethoprim and 800 sulfmethoxizole) 2 tabs initially then b I d X 2 Wks., or until resolved Opermcak et al, Ophthalmology 1992 (safety and efficacy), Rothova et al, Am J Ophthalmol 1993 (comparison to classic and clindamycin regimens) Mepron suspension (Atovaquone 750 mg. [1 tsp] q i d (X 3 months) for toxoplasmic retinochoroiditis in immumocompromised patients Pearson et al, Ophthalmology 1999 QUIZ TIME Recurrences (risk) 16 W/M Slight decrease in VA recently VA = 20/40 (OS), DX =? DDx =? Active lesions are white and fluffy with vitritis While risk appears to decline with increasing time from most recent episode, risk may be accelerated by increasing age (interactive factors). Holland GN, et al., Analysis of recurrence patterns associated with toxoplasmic retinochoroiditis. Am J Ophthalmol ;145(6): LS 49 BF IDDM X 25+ years Questions Comments 1/ 12/ 07 BS runs in the 300s VA 20/20 - OD Scattered H&E No NVD, NVE RTX X 1 Mo. Re for CSME

49 BF IDDM X 25+ years 1/ 12/ 07 VA 20/20 OS NOTE: tortuous retinal vasculatrue, more H & E, some IRMA; moderate NPDR RTC X 1 Mo.

Re for CSME 49 BF IDDM X 25+ years X 6 Mo. Returns in 7 Mo.

Returns in 6 1/2 Mo. 1 /24 /08 VA 20/20 Scattered H&E Mild NPDR; more H & E RTC X 3 Mo. Re for CSME 49 BF IDDM X 25+ years X 12 Mo.

20 49 BF IDDM X 25+ years 1/ 12/ 07 VA 20/20 OS NOTE: tortuous retinal vasculatrue, more H & E, some IRMA; moderate NPDR RTC X 1 Mo. Re for CSME 49 BF IDDM X 25+ years X 6 Mo. Returns in 7 Mo. 8/ 9/ 07 VA 20/20 Scattered H&E Mild NPDR; more H & E RTC X 3 Mo. Re for CSME 49 BF IDDM X 25+ years X 6 Mo. Returns in 7 Mo. 8/9/07 VA 20/20 Scattered H&E Moderate NPDR; tortuous vasculature RTC X 3 Mo. Re for CSME 49 BF IDDM X 25+ years X 12 mo. Returns in 6 1/2 Mo. 1 /24 /08 VA 20/20 Scattered H&E Mild NPDR; more H & E RTC X 3 Mo. Re for CSME 49 BF IDDM X 25+ years X 12 Mo. Returns in 7 Mo. 1 /24/08 VA 20/20 Scattered H&E Moderate NPDR; tortuous vasculature RTC X 3 Mo. Re for CSME 49 BF IDDM X 25+ years X 26 mo. Returns in 13 1/2Mo. 3 /10/09 VA 20/20 Scattered H&E Mild NPDR; more H & E CSME!

49 BF IDDM X 25+ years X 26 Mo. Returns in 13 1/2 Mo.

OS); proliferative changes, too OCT Shows distinct CSME confirming

week OD 51 BF 3/ 11/ 09 OCT Shows distinct CSME confirming week OD 51 BF

21 49 BF IDDM X 25+ years X 26 Mo. Returns in 13 1/2 Mo. 3/ 10/09 VA 20/20 Scattered H&E Mod to Severe NPDR; IRMA, VB CSME (worse OS); proliferative changes, too OCT Shows distinct CSME confirming clinical assessment Plan: Focal laser OS PRP OS Avastin OS Then same X 1 week OD 51 BF 3/ 11/ 09 OCT Shows distinct CSME confirming clinical assessment Plan: Focal laser OS PRP OS Avastin OS Then same X 1 week OD 51 BF 3/ 11/ 09 OCT Shows distinct CSME confirming clinical assessment Plan: Focal laser OS PRP OS Avastin OS Then same X 1 week OD 51 BF 3/ 11/ BF 3/ 11/ BF 3/ 11/ 09

22 51 BF 3/ 11/ 09 Treatment OS first Focal laser to the macula PRP Avastin OD X 1 week Focal laser to the macula Avastin Another option for macular edema is grid laser. Questions Comments 129

Rare Presentation of Ocular Toxoplasmosis

Case Report Rare Presentation of Ocular Toxoplasmosis Rakhshandeh Alipanahi MD From Department of Ophthalmology, Nikookari Eye Hospital, Tabriz University of Medical Sciences, Tabriz, Iran. Correspondence: