1. Grand Rounds January 5, 2007 Jeffrey D. Colburn, M.D., PGY-2 Vanderbilt Eye Institute

2. The Case… CC: New onset blurry vision (x2 days) HPI: 70 yo WF admitted 10 days prior for N/V/failure to thrive s/p Abd surgery –Pain in OS transiently 2 days ago –Like “looking through a dirty windshield” –New floaters OU

3. History Past Ocular Hx –Wears glasses –CEIOL OD Past Med/Surg Hx –Insulinoma, s/p pancreatic enucleation, 8/29/06 –Ventral hernia, 8/06 –CT guided drainage of fluid collection surrounding pancreas (9/21/06) –Home TPN since 10/2/06 –HTN –CAD, s/p MI & CABG –Depression Meds: ASA, Imdur, Cartia, Coreg, Lasix, HCTZ, KCl, Protonix, Pravachol, Naproxen, MVI, Nitro, Ca+D, Lopid, Prozac, Reglan, Vancomycin Allergies: Theodur, Demerol Family Hx –Father – Colon CA –Mother – CHF –Son – DM –Daughter – SLE Social Hx –No Tobacco –Occasional EtOH ROS + Nausea, Vomiting, Fatigue, chronic SOB

4. Exam BCVA: 20/200-1 OU IOP: 15 OD, 16 OS CVF: full OD, superonasal deficit OS Pupils: 4 → 2 OU, no RAPD Motility: Full OU External: WNL

5. Exam SLE LLL: quiet OU Conj: quiet OU K: clear OU A/C: D&Q OU, no cell/flare Iris: Intact Lens: PCIOL OD, 2-3+ NSC OS

7. VA now 20/400 OU

8. Further Images from OS

9. Exam DFE: Vitreous: vitritis OD>OS Disks: hazy view C/D: small cups OU Macula: round white lesion with well defined edges near fovea OD Periphery: similar lesions superiorly & nasally OS Vascular: wnl

10. Differential Diagnosis

11. Infectious –Bacterial endophthalmitis –Fungal endophthalmitis –Toxoplasmosis –Syphilis –CMV retinitis –HZV/HSV retinitis –Nocardia –Tuberculosis Inflammatory/Infiltrative –Sarcoid –Wegener’s –PAN Neoplastic –Large cell lymphoma

12. Additional History Fever spike of 102.7 with tachycardia 4 days prior PICC line removed Cultures grew out Coag Negative Staph and Candida albicans On IV Vancomycin & Diflucan

13. Diagnosis: Endogenous Multifocal Infectious Chorioretinitis – likely staphylococcal due to multifocal nature, recent fever spike, diffuse vitritis

14. Course –Tx with IV Vancomycin, PO Diflucan –Day 3 – Minimal improvement, added PF 1% QID for AC reaction –Week 2 – PF not started, Posterior Synechiae developed OS –Week 4 – No better, new lesions OS, increased vitritis with “string of pearl appearance” VA= 6’/200 E OU → Revised diagnosis: Endogenous Fungal Endophthalmitis

15. Course –Week 4 – Intravitreal injection of amphotericin OU Switched to IV caspofungin and PO voriconazole –Week 5 – PPV, intravitreal inj of Amphotericin OS –Week 6 – PPV, intravitreal inj of Amphotericin OD –Vitreal cultures – no growth OU

16. Candida – most common History of risk factors Mild/Mod inflammation, focal/multifocal yellow- white chorioretinal lesions –May coalesce, forming mushroom shaped nodules extending into vitreous –Classic: “string of pearls” appearance Dx: systemic/intraocular cultures, PPV Relatively favorable outcome for Candida if treated aggressively early. Endogenous fungal endophthalmitis

17. Candidemia Rare before 1950 Incidence in patients with candidemia reported from 28% to 45% Donahue, et al, showed in 1992 that Candida endophthalmitis was rare when properly defined –118 patients, no endophthalmitis, 9.3% chorioretinitis only –Risk factors: visual symptoms, C. albicans species, immunosuppression, multiple + blood cultures Feman, et al (2002): incidence of <2%

18. Treatment Intravenous amphotericin B – first used in 1960 –Significant systemic side effects –Poor intraocular penetration Systemic fluconazole –Better side effect profile –O’Day, et al: Better intraocular penetration –May be effective monotherapy for chorioretinitis –Fungistatic

19. Treatment Vitrectomy –First reported in 1976 –Provides specimen for diagnosis –Removes pathogen load –Improves ocular penetration of systemic tx Intraocular amphotericin B –Potential retinal toxicity, but rarely seen clinically –Used commonly for advanced cases

20. Treatment Vitrectomy with oral fluconazole alone may be an effective option –Christmas & Smiddy (1996): Case series 6 of six eyes PPV and 4-weeks of oral fluconazole Five achieved final VA of 20/40 or better

21. Treatment Intraocular corticosteroid injection is controversial –Theoretically should not alter host defense as no affect on neutrophils –If used, must assure appropriate antimicrobial coverage Intraocular imidazoles may be useful in cases of resistance to therapy, or for Aspergillus PO/IV voriconazole and caspofungin for tx failure

22. Update on our patient –Last visit (1/2/07 – Week 10) –VA: 6/200 OD, 20/60 with correction OS –Inactive punched out scars in both eyes. –Resolved vitritis

23. To Remember Relatively favorable prognosis Keep this diagnosis in mind Early and aggressive therapy Treatment options are expanding

24. References Donahue SP, et al. Intraocular candidiasis in patients with candidemia. Ophthalmology 1994;101:1302-1309. Flynn, HW. The Clinical challenge of endogenous endophthalmitis. Retina 2001;21:572-574. Gupta A, et al. Fungal endophthalmitis after a single intravenous administration of presumably contaminated dextrose infusion fluid. Retina 2000;20:262-268. O’Day DM. Ocular uptake of fluconazole following oral administration. Arch Ophthalmol 1990;108:1006-1008. Smiddy, WE. Treatment outcomes of endogenous fungal endophthalmitis. Current Opinions in Ophthalmology 1998;9:66-70. Snip RC, Michels RG. Pars plana vitrectomy in the management of endogenous Candida endophthalmitis. Williams, MA, et al. Diagnosis and treatment of endogenous endophthalmitis. Ophthalmologica 2006;220:134-136.

25. Thank you