1. A World Away David J. Herren, MD Super Bowl of Grand Rounds August 5, 2016

2. ● 24yo male ○ Tilganga Institute of Ophthalmology  Kathmandu, Nepal ○ 24 hour history of right eye pain, redness, and decreased vision.  Present upon awakening  “Moderate” severity HPI

3. ● POH ○ None ● PMHx ○ None ● Meds ○ None ● NKDA Relevant Medical History ● SH ○ Elementary school teacher ○ Denies tobacco use ○ Occasional EtOH ○ Denies recreational drugs ○ Married with no children ● FH ○ No eye diseases or blindness

4. ● Review of Systems - Negative ○ General ○ Ocular/vision prior to symptoms ○ Auditory ○ Gastrointestinal ○ Cardiovascular ○ Pulmonary ○ Genitourinary ○ Neurologic ○ Musculoskeletal ○ Psychiatric ○ Dermatologic Relevant History continued

5. ExamODOS BCVACF20/20 Pupils4 -> 2mm, No RAPD, ?sluggish4 -> 2mm, No RAPD VFFTC (with effort)FTC MotilityFull Ta8 mmHg14 mmHg

8. SLEODOS ExtWNL L/Lmild UL and LL edemaIntact C/S3-4+ InjectionW&Q KFine KP, otherwise clearClear A/C 3-4+ cell/flare, 1mm hypopyon D&Q I Round pupil, fibrin/membrane Regular LClearClea Ant Vit3+ cellsquiet

9. DFEODOS VitDense cellsClear DBare visibility0.3 c/d, pink and sharp MNo viewFlat VNo viewNormal C&C PNo viewNo t/h/d

10. DFE

11. B Scan OD

12. ● Tap and inject o Intravitreal injection  Vancomycin 1mg/0.1ml  Amikacin 0.4mg/0.1ml  Dexamethasone 0.4mg/0.1ml o Subconjunctival injection  Vancomycin 25mg/0.5ml  Amikacin 25mg/0.5ml  Dexamethasone 6mg/0.25ml Next Step

13. Tap & Inject Description: “Thick, greenish, turbid fluid”

14. ● Vigamox Q1 hour while awake OD ● Pred Forte Q 30 mins while awake OD ● Atropine TID OD ● Ciprofloxacin ung QHS OD ● Ibuprofen PO Q4hours PRN pain ● RTC 1 day Plan

15. ● A little less pain ● Able to see more light OD Day 2

16. SLEOD- ExtWNL- L/LLid edema stable- C/S2-3+ Injection- KFine KP, otherwise clear- A/C 2+ cell & flare, trace hypopyon - IRound, Fibrin- L Retracted membrane on ant lens capsule -

17. DFEOD- VitLess dense cells- DImproved visibility- MGrossly flat- VVisible- PGrossly normal-

18. ● ¨ Vitreous sample o Gram stain  Gram-positive cocci single, pairs, & groups  WBCs 1-3/HPF o Giemsa stain  WBCs 1-2/HPF o KOH preparation  No fungal elements seen Follow Up

19. SLEOD- ExtWNL- L/LIntact- C/STrace Injection- KRare fine KP, clear- A/C1+ cell, No hypopyon- I Round, No fibrin/membrane - L No membrane on ant lens capsule, clear - Day 4 VA - CF

20. Laboratory Results ● Vitreous culture and sensitivities o Staphylococcus aureus isolated o Sensitive to:  Amikacin  Chloramphenicol  Ciprofloxacin/Moxifloxacin  Cefazolin  Vancomycin  Tobramycin

21. Repeat Tap & Inject ● Vitreous tap: Clear and watery ● Intravitreal injection o Vancomycin 1mg/0.1ml o Dexamethasone 0.4mg/0.1ml ● Subconjunctival injection o Vancomycin 25mg/0.5ml o Dexamethasone 6mg/0.25ml

22. SLEOD- ExtWNL- L/LIntact- C/SSmall SCH but quiet- Kclear- A/C0.5-1+ cells- IRound- L clear with few pigment deposits on ant capsule - Day 7 - VA PH = 20/60

23. Laboratory Results ● Repeat vitreous culture and sensitivities oNGTD ● Continue current regimen

24. SLEOD- ExtWNL- L/LIntact- C/SSmall SCH but quiet- Kclear- A/C0.5+ cells- IRound- L clear with few pigment deposits on ant capsule - Day 11 - VA PH = 20/30

25. ● Vancomycin 50mg/mL Q2 hours WA OD ● Vigamox Q2 hours while awake OD ● Pred Forte Q 2 hours while awake OD ● Ciprofloxacin ung QHS OD ● Atropine BID OD ● PFAT’s TID OD ● RTC 6 days Plan

26. SLEOD- ExtWNL- L/LIntact- C/Ssmall, resolving SCH, quiet- Kclear- A/C0.5+ cells- IRound- L clear with few pigment deposits on ant capsule - Day 14 - VA = 20/30

29. ● Vancomycin 50mg/mL Q4 hours WA OD ● Vigamox Q4 hours while awake OD ● Pred Forte Q 4 hours while awake OD ● Ciprofloxacin ung QHS OD ● Atropine BID OD ● PFAT’s TID OD ● RTC 7 days Plan

31. ● Infectious o Bacterial endophthalmitis o Viral/Herpetic o TB o Syphilis o Toxoplasma variant o Toxocariasis ● Inflammatory o Behcet’s Disease o HLA B27 o Sarcoidosis o VKH-like (?unilateral) o Posterior scleritis Differential Diagnosis ● Malignancy/Masquerade o Lymphoma/Leukemia ● Trauma o Prior IOFB o SO ● Medication ● Idiopathic

32. ●First described in 1978 by Malla ○ “Endophthalmitis probably caused by Tossock moth” ○ Pokhara Valley of Nepal ○ 13 cases ● Seasonal hyperacute panuveitis of unknown etiology (SHAPU) ○ Upadhyay in 1984 ○ Other regions of Nepal ○ 12 cases ●Only found in Nepal ● Typically Unilateral ● Hyperacute Endophthalmitis vs Panuveitis ○ Hours to days Seasonal Hyperacute Panuveitis 1. Malla OK. Endophthalmitis probably caused by Tussock moth. In: Proceedings of first National Seminar on Prevention of Blindness; 1978. p. 44 2.Upadhyay MP, Rai NC, Ogg JE, Shrestha BR. Seasonal hyperacute panuveitis of unknown etiology. Ann Ophthalmol 1984; 16:38–44. 3.Manandhar A. Seasonal hyperacute panuveitis: an update. Curr Opin Ophthalmol. 2011 Nov;22(6):496-501. doi: 10.1097/ICU.0b013e32834bcbf4. Review. PubMed PMID: 21986882.

33. ● Redness, photophobia ○ Minimal pain ● Dramatic loss of vision ○ “within an hour” ● White pupils the next day ○ “Red eye and white pupil” ●Hypopyon ● Fibriniod exudate in AC ● Low IOP ● Later: ○ AC shallows ○ Progresses to “malignant hypotension” ● Historically, poorly responsive to therapy SHAPU 1.Manandhar A. Seasonal hyperacute panuveitis: an update. Curr Opin Ophthalmol. 2011 Nov;22(6):496-501. doi: 10.1097/ICU.0b013e32834bcbf4. Review. PubMed PMID: 21986882.

34. ● More common in children ● Males = Females ● Moths are suspected cause/vector ○ Tussock moth ○ Gazalina chrysolopha  Nepal, India, Bhutan, Burma, China, and Taiwan *Not confirmed in experimental models ● Outbreaks every other year ○ 2005, 2007, 2009,etc. ○ September - December ○ 2008 and 2010 had small outbreaks ○ Two broods (summer and fall) ○ Parallels Gazalina populations SHAPU 1.Manandhar A. Seasonal hyperacute panuveitis: an update. Curr Opin Ophthalmol. 2011 Nov;22(6):496-501. doi: 10.1097/ICU.0b013e32834bcbf4. Review. PubMed PMID: 21986882. 2.Upadhyay MP, Rai NC, Ogg JE, Shrestha BR. Seasonal hyperacute panuveitis of unknown etiology. Ann Ophthalmol 1984; 16:38–44

35. ● Moths? ● 2007 Outbreak: ○ 2 of 20 cases  multiple tiny brown-colored hairs seen in corneal stroma ●2009 Outbreak: ○ 5 of 55 cases had similar fine brown hairs ○ 1 hair was see floating in anterior vitreous in 1 of the 5 eyes ○ Iris atrophy in 4 cases ○ Decreased corneal sensation in 15 cases  Moths as vector for viral etiology? ● Gazalina does have ‘flechettes’ ○ brown colored barbed spines on the abdomen SHAPU 1.Manandhar A. Seasonal hyperacute panuveitis: an update. Curr Opin Ophthalmol. 2011 Nov;22(6):496-501. doi: 10.1097/ICU.0b013e32834bcbf4. Review. PubMed PMID: 21986882.

36. ●Byanju, et al. (2003) ○ 14 eyes with SHAPU  Early vitrectomy  50% had restoration of 20/200 VA or better ● Kathil, et al. (2005) ○ Reported isolation of VZV in aqueous by immunofluorescence ○ PCR for VZV was negative ○ Completely recovered with:  Acyclovir IV/PO, cefotaxime PO, prednisone PO ● Manandhar, et al. (2008) ○ First report on bacterial growth in vitreous cultures in 3 of 6 eyes ○ 2 Strep. Pneumoniae ○ 1 Acinetobacter sp. ○ Treated with intravitreal vancomycin, amikacin, & dexamethasone  Plus core vitrectomy, topical/oral steroids Recent Developments 1.Byanju RN, Pradhan E, Sapkota YD. Visual outcome of vitrectomy in seasonal hyperacute panuveitis. Kathmandu Univ Med J 2003; 1:121–123 2.Kathil P, Biswas J, Gopal L. Demonstration of varicella zoster virus in a case of presumed seasonal hyperacute panuveitis. Indian J Ophthalmol 2005; 53:270–272 3.Manandhar A, Paudel G, Rai CK, et al. Seasonal hyperacute panuveitis: recent scenario in Nepal. Nepal Med Coll J 2008; 10:196–198.

37. ●Shrestha, et al. (2010) ○ 20 eyes with SHAPU from the 2007 outbreak  Only 2 cases reported moth contact (direct or environment)  Treated with intravitreal +/- subconjunctival ● Vancomycin ● Amikacin ● Dexamethasone  43% regained 20/60 vision or better ● 33% only received repeated subconjunctival steroids  No eyes received vitrectomy ● Smits, et al. (2012) ○ PCR on vitreous samples from 10 eyes with SHAPU ○ Presence of anellovirus in 2 samples  Discovered in 1990’s  Associated with MS, SLE, hepatitis, and asthma. Recent Developments 1.Shrestha E. A profile and treatment outcome of seasonal hyper-acute panuveitis. Nep J Ophthalmol 2010; 2:35–38 2.Smits SL, Manandhar A,et al. High prevalence of anelloviruses in vitreous fluid of children with seasonal hyperacute panuveitis. J Infect Dis. 2012 Jun 15;205(12):1877-84. doi: 10.1093/infdis/jis284. Epub 2012 Apr 5. PubMed PMID: 22492851.

38. ● Adult ● Significant improvement ● Cultured Staph aureus ● No contact with moths ● No significant hypotony ● No vitrectomy Our Patient

39. ●Seasonal Hyperacute Panuveitis oEndophthalmitis vs Panuveitis o Hyperacute o Often visually devastating o Primarily affects children o Only described in Nepal o Every other year o ?Moth association Summary