Cytomegalovirus retinitis and treatment

1. CMVR-Related
Retinal Detachment
Nawat Watanachai
RCOPT 2014
Bangkok

2. AIDS : in the past
• pre-HAART era : 1981-1995
• AIDS : fatal disease
• CMVR : CD4 <100/ml
• CMVR :*
• 25-42% of AIDS
• strong predictor of mortality
• aim of eye treatment :
• short-term ctrl of retinitis
• RRD 40% of CMVR eyes
• —> blind —>dead
• * Bowen EF, Wilson P, Cope A, et al. Cytomegalovirus retinitis in AIDS patients: Influence of cytomegaloviral load on response to
ganciclovir, time to recurrence and survival. AIDS 1996, 10(13):1515-20.

3. AIDS : in the present
• HAART era : 1996-now
• AIDS : NOT a fatal disease
• newer medication
• screen if CD4<100/ml
• oral valgancyclovir or others
• pts live a longer life
• stop/ slow the progression of CMVR
• incidence decrease 80%*
• * Skiest DJ. Cytomegalovirus retinitis in the era of highly active antiret- roviral therapy
(HAART). Am J Med Sci. 1999;317:318–335.

4. AIDS : in the present
• HAART era : 1996-now
• HAART-treated puts
• lower incidence of RD 40%—>3.2% of CMVR eyes**
• disease progression***
• 2nd eye involvement***
• aim of treatment : long-term vision preservation
** Jabs DA, van Natta ML, Thorne JE, et al. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 2. Second eye
involvement and retinal detachment. Ophthalmology. 2004;111: 2232–2239.
*** Jabs DA, van Natta ML, Thorne JE, et al. Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 1. Retinitis
progression. Ophthalmology. 2004;111:2224–2231.

5. then,
why CMVR is
still be a serious
problem?

6. why CMVR is still be a serious problem?
• CMVR related visual loss is usually severe
• WHO : blindness = VA<3/60
• CMVR : HM or worse in 89% of CMVR-related blind eyes
• 21-36% already had blind eye when eye doc gave dx of CMVR*
• non-ambulatory vision in the young
1. Heiden D, Ford N, Wilson D, Rodriguez WR, Margolis TM, et al: Cytomegalovirus retinitis: the neglected disease of the AIDS pandemic. PLoS Med 2007, 4(12):e334.
2. Shi Y, Lu H, He T, Yang Y, Liu L, et al: Prevalence and Clinical Management of Cytomegalovirus Retinitis in AIDS patients in Shanghai, China. BMC Infectious Diseases .
3. Ausayakhun S, Watananikorn S, Ngamtiphakorn S, Prasitsilp J: Intravitreal foscarnet for cytomegalovirus retinitis in patients with AIDS. J Med Assoc Thai 2005, 88:103-107.
4. Ausayakhun S, Yuvaves P, Ngamtiphakorn S, Prasitsilp J: Treatment of cytomegalovirus retinitis in AIDS patients with intravitreal ganciclovir. J Med Assoc Thai 2005, 88(Suppl 9):S15-S20.

7. why CMVR is still be a serious problem?
• second most common cause of blindness in the
northern thailand*
• HIV pts = 2% of the general population*
• * Pathanapitoon K, Ausayakhun S, Kunavisarut P, Wattananikorn S, Leeungurastien T, Yodprom R,
Narongjunchai D, Rothova A: Blindness and low vision in a tertiary ophthalmologic center in
Thailand: the importance of cytomegalovirus retinitis. Retina 2007, 27(5):635-640.

8. why CMVR is still be a serious problem?
• CMVR-RRD
• higher rate of failure after treating by standard
techniques of SBP, Pneumatic retinopexy, PPV, FGX
• why?

9. WHY CMVR-RRD is so stubborn?
• factors
• large areas of full thickness retinitis —
> full thickness retinal necrosis
• multiple RBs in multiple quadrants
• frequent posterior location of the RBs
• hard to identify RBs in areas of
necrotic detached retina
• Brar M, Kozak l, et al: Vitreoretinal interface abnormalities in healed cytomegalovirus retinitis. Retina 2010;30(8):1262-6.
• Cavan P, Chris OR, et al: Optical coherence tomography in the diagnosis and management of uveitis. Can J Ophthalmol2014:49(1):18-
29.

10. WHY CMVR-RRD is so stubborn?
• factors
• laser not works well in the atrophic areas
• vitritis —> persistent VR traction over the healed areas
• ERM
• vitreoretinal gliosis
• vit traction, esp. on the rims
• ongoing nature of retinitis
• Brar M, Kozak l, et al: Vitreoretinal interface abnormalities in healed cytomegalovirus retinitis. Retina 2010;30(8):1262-6.
• Cavan P, Chris OR, et al: Optical coherence tomography in the diagnosis and management of uveitis. Can J
Ophthalmol2014:49(1):18-29.

11. treatment : nonRD-related CMVR
• IV ganciclovir/ foscarnet/ cidofovir
• oral valganciclovir
• intravit ganciclovir inj*
• the most cost effective
• usual : 0.2-4 mg/0.1ml*,**
• safe : 6 mg
• NOOOO! : 40 mg
• intravit foscarnet(yes?)/ cidofovir(no)
• intravit ganciclovir implant
• *Stewart M, et al. : Optimal management of cytomegalovirus retinitis in patients with AIDS: Clin Ophthal: open access
• **Yutthitham K, Ruamviboonsuk P. The high-dose, alternate-week intravitreal ganciclovir intentions for cytomegalovirus
retinitis in AIDS patients on HAART. J Med Assoc Thai. 2005, 88:63-8.

12. Treatment : RD-related CMVR
• choices of RRD treatment
• laser retinopexy
• SBP
• pneumatic retinopexy
• PPV+gas?
• PPV+SOI

13. Treatment : RD-related CMVR
• choices of RRD treatment
• laser retinopexy
• SBP
• pneumatic retinopexy
• PPV+gas?
• PPV+SOI

14. laser :
walling off
• conditions :
• macula on RRD, not close to post. pole
• wide/ many areas of atrophic retina
• 3 rows of confluent laser burns
• place in healthy retina surrounding RD, whole
area of necrotic healed retinitis

15. laser : walling off
• may failed due to
• vitreous contraction (incomplete PVD)
• too large and bullies
• advancing CMVR
• success
• 78.2% in eyes without RRD*
• 57-68% in eyes with RRD**
• * Althaus C, Loeffer KU, Schimkat M, et al. Prophylactic argon laser coagulation for rhegmatogenous retinal detachment in AIDS patients with
cytomegalovirus retinitis. Graefes Arch Clin Exp Ophthalmol. 1998;236:359-64.
• **Vrabec TR. Laser photocoagulation repair of macula-sparing cytomegalovirus-related retinal detachment. Ophthalmic. 1997;104:2062-7.
• **Davis JL, Hummer J, Feuer WJ. Laser photocoagulation for retinal detachments and tears in cytomegalovirus retinitis. Ophthalmology, 1997;104:2053-
60.

16. Treatment : RD-related CMVR
• choices of RRD treatment
• laser retinopexy
• SBP
• pneumatic retinopexy
• PPV+gas?
• PPV+SOI

17. Scleral Buckle Procedure
• usually failed in advanced cases
• hard to identify RBs in the atrophic areas
• SBP should cover all areas of atrophic retina
• higher risk of accident
• use only in selected cases
• localized anterior RRD

18. Treatment : RD-related CMVR
• choices of RRD treatment
• laser retinopexy
• SBP
• pneumatic
retinopexy
• PPV+gas?
• PPV+SOI

19. • pneumatic retinopexy

20. Treatment : RD-related CMVR
• choices of RRD treatment
• laser retinopexy
• SBP
• pneumatic retinopexy
• PPV+gas?
• PPV+SOI

21. PPV+gas
• mixed results
• depended on case selection
• conditions
• simple RRD
• RB in 1-2 quadrants
• superior breaks
• no/ few PVR
• inacive CMVR
• Canzano JC, Morse LS, Wendel RT. Surgical repair of cytomegalovirus-related retinal detachment without silicone
oil in patients with AIDS. Retina. 1999;19:274-8.

22. Treatment : RD-related CMVR
• choices of RRD treatment
• laser retinopexy
• SBP
• pneumatic retinopexy
• PPV+gas?
• PPV+SOI

23. PPV+SOI
• 1987 Freeman and assocites :
• successful treatment of PPV+SOI
• Freeman WR, HenderlyDE, Wan WL, etal:Prevalence,pathophysiology,andtreat-
mentofrhegmatogenousretinaldetachmentintreatedcytomegalovirusretinitis.AmJ Ophthalmol 1987; 103:527-536.

24. 2 Irvine AR. The treatment of retinal detachment due to CMV retinitis in AIDS. Trans Am Ophthalmol Soc 1991;89:
34967.
3 Dugel PU, Liggett PE, Lee MB, Ziogas A, Forster DJ, Smith RE, et al. Repair of retinal detachment caused by
cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. Am J Ophthalmol 1991;112: 235–42.
4 Sidikaro Y, Silver L, Holland GN, Krieger AE. Rhegmato- genous retinal detachments in patients with AIDS and
necrotizing retinal infections. Ophthalmology 1991;98:129– 35.
5 Freeman WR, Quiceno JI, Crapotta JA, Listhaus A, Mungria D, Aguilar MF. Surgical repair of rhegmato- genous retinal
detachment in immunosuppressed patients with cytomegalovirus retinitis. Ophthalmology 1991;99: 466–74.
6 Kupperman BD, Flores-Aguilar M, Quiceno JI, Capparelli EV, Levi L, Mungria D, et al. A masked prospective evalu-
ation of outcome parameters for cytomegalovirus-related retinal detachment surgery in patients with acquired immune
deficiency syndrome. Ophthalmology 1994;101: 46–55.
7 LimJI,EngerC,HallerJA,CampochiaroPA,MeredithTA, de Bustros S, et al. Improved visual results after surgical repair of
cytomegalovirus-related retinal detachments. Ophthalmology 1994;101:264–9.
8 Garcia RF, Flores-Aguilar M, Quiceno JI , Capparelli EV, Mungria D, Kupperman BD, et al. Results of rhegmato-
genous retinal detachment repair in cytomegalovirus retinitis with and without scleral buckling. Ophthalmology
1995;102:236–45.
9 Nasemann JE, Mutsch A, Wiltfang R, Klauss V. Early pars plana vitrectomy without buckling procedure in cytomega-
lovirus retinitis-induced retinal detachment. Retina 1995; 15:111–6.
10 Regillo CD, Vander JF, Duker JS, Fischer DH, Belmont JB, Kleiner R. Repair of retinitis-related retinal detachments
with silicone oil in patients with acquired immunodefi- ciency syndrome. Am J Ophthalmol 1992;113:21–7.
11 Dowler JGF, Towler HMA, Mitchell SM, Cooling RJ, Lightman SL. Retinal detachment and herpesvirus retinitis in
patients with AIDS. Br J Ophthalmol 1995;79:575–80.

25. PPV+SOI
• 1. Singh R, Bhalekar S, et al: Outcome of surgery in post-
cytomegalovirus retinal detachment: Indian J Ophthalmol.
2013:61(11)636-9.
• 2. Gore SK, Gore DM, Chetty K, Visser L:
Cytomegaloviral retinitis-related retinal detachment:
outcomes following vitrectomy in the developing world: Int
Ophthalmic. 2014:34(2):205-10.

26. PPV+SOI
• highest success rates
• became standard treatment for advanced CMVR-related RRD
• Freeman WR, HenderlyDE, Wan WL, etal:Prevalence,pathophysiology,andtreat-
mentofrhegmatogenousretinaldetachmentintreatedcytomegalovirusretinitis.AmJ Ophthalmol 1987; 103:527-536.

27. PPV+SOI : problems
• 5-7D hyperopic shift
• usually decreased by 1-4D when SBP was done
• 18-53%risk of redetachment
• increased in eyes after silicone oil removal
• Dave V, Mathai A, Pappuru R. Results of silicone oil removal in post-cytomegalovirus retinitis-related retinal
detachment. J Ophthal Inflame Infect. 2012;2:153-155.
• Davis J. Removing silicone oil from eyes with cytomegalovirus retinitis. Am J Ophthalmol. 2005;140:900–902.
• Morrison VL, Labree LD, Azen SP, et al: Result of silicone oil removal in patients with cytomegalovirus retinitis
related retinal detachments. Am J Ophthalmic. 2005;130:786-793.

28. PPV+SOI : problems
• high incidence of cataract after PPV+SOI
• PCO in pseudophakic
• poor retina visualisation
• glaucoma
• Tanna AP, Kempen, JH, et al. Incidence and management of cataract after retinal detachment
repair with silicone oil in immunocompromised patients with cytomegalovirus retinitis. Am J
Ophthalmic. 2008: 1009-15.

29. Treatment :
nonRD-related CMVR
• early detection : screening
• CD4<100/ml
• all including asymptomatic ones*
• telemedicine can work well*
• Treatment
• nonRD-related :antiviral Rx
• * Gellrich MM, Lagreze WD, Rump JA, Hansen LL: [Indications for eye examination of HIV patients - screening parameters for cytomegalovirus
retinitis]. Klin Monbl Augenheilkd 1996, 209(2-3):72-8.
• ** Ausayakhun S, Skalet AH, Jirawison C, Ausayakhun S, Keenan JD, Khouri C, Nguyen K, Kalyani PS, Heiden D, Holland GN, Margolis TP:
Accuracy and Reliability of Telemedicine for Diagnosis of Cytomegalovirus Retinitis. Am J Ophthalmol 2011.

30. Treatment :
RD-related CMVR
TREATMENT MACULA RRD
LASER on not involve posterior pole
SBP on/off simple/ unable position
PPV+GAS on/off
simple/ few breaks/ atrophic areas
located in 1-2 adjacent sup.
quadrants
PPV+SOI
+/-SBP
on/off difficult/ unable position