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Cover letter
Friday, January 10, 2013
Dear Dr. Editor-in-Chief, Chinese Medical Journal
Non-infectious endophthalmitis after vitrectomy
Thank you for your valuable suggestions. We are pleased to submit the revised version of the
above-titled manuscript.
Point-by-point changes:
1.
Intravitreal response factor can still not be ruled out.
Yes, this factor can not be ruled out. I’ve already inserted to the text. See page 7, last paragraph,
line 7.
2.
To add more details in the course of treatment in order to get more clinical guidance
I have added more details about the treatment. Please see page 5, last paragraph.
3.
Another modification: change conjunctiva injection to conjunctival hyperemia. See page 6, last
paragraph, line 5.
All revisions are in red font.
Thank you and best regards!
Wenbin
Wenbin Wei, M.D., PhD..
Professor of Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University,
Beijing Ophthalmology and Visual Science Key Lab, Beijing, China.
No.1 Dongjiaominxiang Street, Beijing 100730, China
Email: [email protected]
1
Title Page
Original article
Non-infectious endophthalmitis after vitrectomy
1
Yao Huang, MD & PhD; 2Ning Cheung, MD; 1Bei Tian, MD & PhD; 1Wenbin Wei, MD &
PhD
1Beijing
Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing Ophthalmology
& Visual Science Key Lab, Beijing, China, 100730.
2Department
of Ophthalmology & Visual Sciences, the Chinese University of Hong Kong.
Corresponding Author: Wenbin Wei, MD & PhD.
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology
and Visual Science Key Lab, Beijing, China.
No.1 Dongjiaominxiang Street, Dongcheng District, Beijing, China, 100730
Email: [email protected]
Tel: +86-10-58269152
Disclosure: The authors have no financial interest to declare regarding to this article.
2
Abstract
Objectives: To report a series of patients occurring non-infectious endophthalmitis after pars plana
vitrectomy in the same two operation rooms during the same period.
Methods: Medical records of patients who presented with severe non-infectious endophthalmitis
following vitrectomy between May 13 and June 8, 2011, were reviewed.
Results: Ten patients were identified with severe non-infectious endophthalmitis, presenting 1 day after
pars plana vitrectomy. Three eyes (30%) had previous intraocular surgeries. Four eyes (40%) had
proliferative diabetic retinopathy. One eye (10%) had branch retinal vein occlusion. One eye (10%) had
rheumatogenous retinal detachment. One eye (10%) had macular hole and cataract and had combined
phacoemulsification, intraocular lens implantation and pars plana vitrectomy. All the patients were
initially managed with topical and/or oral steroids. Only two patients had intravenous antibiotics
because of the atypical presentation. One eye had paracentesis because of high intraocular pressure and
the aqueous sample was sent for microbiological examination. The culture of the aqueous, air in the
operation room, the swab from hand of surgeons, infusion fluid and vitrectomy effluent were all
negative for bacteria and fungi. The inflammation regressed rapidly after the initial treatment.
Conclusions: Intraocular surgery history, poor general health status, longer operation time and more
surgical procedures are the risk factors for non-infectious endophthalmitis after vitrectomy. It reacts
effectively to steroids.
Key words: non-infectious, endophthalmitis, pars plana vitrectomy
3
Endophthalmitis is a serious intraocular inflammatory disease broadly categorized as infectious, sterile,
or pseudophthalmitis.[1] The latter two belong to non-infectious endophthalmitis which generally
manifest within a few days of intraocular surgery and present as a painless red eye with marked anterior
chamber and vitreous inflammation.[2] Non-infectious endophthalmitis was reported to occur after
cataract surgery[3] and intravitreal injections.[4,5] To the best of our knowledge, it has not been reported
to happen after vitrectomy. The purpose of this paper is to report on the clinical findings and
management of ten patients who developed severe non-infectious endophthalmitis early following pars
plana vitrectomy.
Methods
After approval of the institutional review board of Beijing Tongren hospital, the medical charts of all
patients occurring non-infectious endophathalmitis after pars plana vitrectomy between May 13 and
June 8, 2011, were retrospectively reviewed.
We defined the non-infectious endophthalmitis after vitrectomy in this study as rapid onset,
significant anterior chamber reaction (4 to 5+ cells or hypopyon), and the lack of vitritis and pain. The
data collected include age and sex of each patient, side of the affected eye, date of surgery, and
indication for vitrectomy. Presentation and diagnostic data were recorded as well, including date of
presentation, visual acuity on presentation and intraocular pressure, presenting symptoms and signs,
and initial management and microbiology results. The patients’ clinical courses were recorded, including
the number of steroid usage, and the use of other medication or surgical interventions, as well as the
duration of remission.
Results
A total of 10 patients were included in this study. The average age of patients at the time of presentation
was 49 (ranging from 30 to 69) years old. There were 7 women (70%) and 3 men (30%). The indications
for vitrectomy included proliferative diabetic retinopathy (PDR, 4 patients, 40%), recurrent retinal
detachment (2 patients, 20%), rheumatogenous retinal detachment (RRD, 1 patient; 10%), silicone oil
tamponade (1 patients; 10%), branch retinal venous occlusion (BRVO, 1 patient; 10%), and macular hole
combined with cataract (1 patient; 10%). Preoperation best corrected visual acuity ranged from hand
motion to 1/20.
In this event, the affected patients were operated under local anesthesia in the same two
4
operations rooms between May 13 and June 8, 2011. During this period, 61 vitrectomy were done in
total. Before surgery, all the patients routinely got prophylactic antibiotic eye drops, tobramycin eye
drops four times a day for at least 3 days. A standard 3-port 20-gauge pars plana vitrectomy was
performed in 9 patients. One patient with macular hole had 23-gauge pars plana vitrectomy. Two
patients had Phacoemulsification and/or intraocular lens implantation at the same time because of
cataract which interfered with vitrectomy. Nine patients had epiretinal membrane peeled. In the patient
of macular hole, inner limiting membrane was removed without any use of staining agents, such as
triamcinolone or indocyanine green. For the retinal detachment cases, perfluorocarbon liquid and/or
gas-fluid exchange was used to reattach the retina, and endolaser photocoagulation or cryotherapy was
then performed around the retinal breaks. One patient had scleral buckling at the same time. At the end
of the surgical procedure, silicone oil or C2F6 was injected.
On post operative day 1, these ten patients had a severe cellular response in the anterior chamber.
Visual acuity (VA) ranged from hand motion to light perception. Four patients (40%) presented with
ocular hypertension. Of these, three patients with intraocular pressure (IOP) lower than 30mmHg, which
were satisfactorily controlled by topical treatment. Only one patient had an IOP higher to 45 mmHg,
accompanied by corneal edema and hypopyon. Paracentesis was carried out to reduce IOP and aqueous
was sent for microbiological assessment (culture and sensitivity). The cornea was clear in 6 patients
(60%), while only mild corneal edema was noted in 3 eyes, severe edema in 1 eye which cleared after
paracentesis. Eight patients (80%) had a hypopyon, among which five (50%) had a very dense white
plaque precipitated behind cornea.
All 10 patients were treated with local steroids. Six patients (60%, case 2,3,4,6,7,8) were treated
with periocular injection of dexamethasone (2.5mg) for three days. One patients (10%, case 9) got
periocular injection of dexamethasone (2.5mg) for only one day combined with topical prednisolone
acetate eye drops every 10 min for one hour, three hours per day. One patient (10%, case 10) got topical
prednisolone acetate eye drops alone. One patient (10%, case 1) got topical prednisolone acetate eye
drops, periocular injection of dexamethasone (2.5mg) and tobramycin (20000u) for seven days, and
prophylaxis intravenous antibiotics for three days because of the atypical presentation. One patient (10%,
case 5) got oral prednisolone acetate, periocular injection of dexamethasone (2.5mg) and tobramycin
(20000u), and prophylaxis intravenous antibiotics for seven days, because it was the first case of this
ourbreak. Only 1 patient (case 10) got panracentesis and microbiological examination. The aqueous
culture was negative for bacteria and fungi.
At the same time, air in the operation room, the swab
5
from hand of surgeons, the infusion fluid and the vitrectomy effluent were randomly sent for
microbiological examination. The culture was also negative for bacteria and fungi.
All the patients showed marked improvement in their clinical appearance after initial treatment.
The anterior chamber fibrin was absorbed quickly (Figures 1,2 show representative examples). Table 1
provides a summary of the clinical course.
Discussion
Non-infectious endophthalmitis was reported to happen associated with trypan blue use in cataract
surgery[3] It was also occurred after intravitreal injection, such as, triamcinolone injection for intraocular
inflammation and associated macular edema
[1,2],
bevacizuma[5,6] or ranibizumad[7] injection for
inhibition of neovascularization. While non-infectious endophthalmitis after vitrectomy is a rare event, it
has not been reported to outbreak in literature. Infectious endophthalmitis after vitrectomy has a very
low incidence, ocurring somewhere between 0.040%~0.150%.[8,9,10]. But till now, vitretomy has been
recognized as the most effective way to treat intraocular inflammation, especially combined with silicone
oil tamponade. The silicone oil has a good inhibition effect and can inhibit the growth of residual
bacteria in the vitreous cavity. Vitrectomy with silicone oil tamponade is an effective anti-infective
therapy.
[11,12]
So the incidence of infectious endophthalmitis is extremely rare after vitrectomy,
especially combined with silicone oil tamponade.
Given the clinical symptoms and signs of our patients, acute post-operative infectious
endophthalmitis had to be ruled out. However in our cases, the likelihood of an infectious etiology is
very unlikely. Non-infectious endophthalmitis generally manifests as a painless red eye with very
prominent anterious chamber reaction. All of our patients did not complain obvious pain and purulent
discharge. Signs included eyelid edema and conjunctival hyperemia were mild. Hypopyon appeared so
rapidly. All the patients were administrated of local and/or systemic steroids and the inflammation
regressed rapidly accordingly. Only two of the eyes (case 1 and 5) received intravenous administration of
antibiotics during their courses. In case 1, antibiotics was prophylaxis used because it was the first case
of this outbreak with apparent hypopyon. In case 5, the hypopyon formed as a large dense white plaque
behind the cornea (figure 1), so antibiotics was administrated because of the atypical presentation. The
idea results of the above diagnostic treatment strategies make the diagnosis of infectious
endophthalmitis unlikely.[13] Microbiologic culture of case 10, air in the operation room, the swab from
hand of surgeons, the infusion fluid and the vitrectomy effluent were all negative for bacteria and fungi
6
which was consistent with the above clinical findings, suggesting a non-infectious cause. Although a
negative culture does not rule out an infectious etiology,[14] vitreous sampling for microbiological
assessment is the most reliable way to differentiate infectious endophthalmitis and non-infectious
endophthalmitis. In our cases, we have not done vitreous tap in any of the ten eyes, because all of the
ten eyes had vitreous tamponade (6 was silicone oil, 4 was C2F6). In the case of vitreous tamponade,
especially silicone oil, the vitreous tap and microbiological assessment is not much important.
Alternatively, toxic anterior segment syndrome (TASS) should be considered in the differential
diagnosis. TASS, as its name implies, affects only the anterior segment of the eye. It occurs when a
noninfectious toxic agent enters the anterior segment during surgery and causes an inflammatory
response with increased leukocytes and sometimes hypopyon.[15,16] It mostly occurs after cataract
surgery. However, recent literatures reported that vitrectomy may also cause the occurrence of TASS.[17]
TASS has an early onset, usually within 24 h after surgery. The visual acuity is usually compromised to the
counting fingers level with profound limbus to limbus corneal edema.[15,16] In contrast to TASS, 9 of our
cases the cornea remained transparent or mild edema. Only 1 patient had obvious cornea edema
because of high IOP, and was transparent again after IOP reduced to normal. This made the diagnosis of
TASS unlikely.
Non-infectious endophthalmitis developing upon surgery may be caused by a multifactorial process
or an interindividual variable response to a common factor as a hypersensitivity reaction. Infusion fluid
may be sterile, yet contain endotoxins from killed bacteria. This could cause postoperative sterile
endophthalmitis.[18] The oxidative metal ions residual on the equipments or in the catheters during the
process of disinfection may be the underlying cause of inflammation reaction post surgery.[19]
Non-infectious endophthalmitis was also reported to occur after intravitreal administration of
triamcinolone.[1,2] At the same time, the intravitreal responsive factor can still not be ruled out. In this
study, none of the ten cases used triamcinolone during surgery, so the toxic reaction of triamcinolone
can be ruled out. Previous intraocular surgery, uveitis, poor general health status, longer operation time
and more complicated surgery have been reported to be risk factors for non-fectious
endophthalmitis.[20,21] As in our patients, three eyes (30%) had previous intraocular surgeries. Four eyes
(40%) were proliferative diabetic retinopathy. Diabetes patients have relatively stronger reaction after
stress, such as surgery, trauma et al. Two eyes (20%) got vitrectomy combined with phacoemulsification,
and/or intraocular lens implantation. Among these ten cases, four eyes (40%) had endolaser
photocoagulation. Four eyes (40%) got endolaser photocoagulation and extraocular cryotherapy. The
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combined surgery made the surgical process more complicated and made the anterior chamber reaction
more severe. The average operation time was 80 minutes (range, 50 to 120 minutes). The most severe
case (case 5) and the anterior chamber paracentesis case (case 10) both had the longest surgery time (2h)
among our cases. Case 6 had the shortest surgery time (50min) which indeed had the mildest anterior
chamber reaction post vitrectomy. (Table 1)
The exact cause of this outbreak of acute non-infectious inflammatory reaction has still not been
clearly established. The conclusion was reached that intraocular surgery history, poor general health
status, longer operation time and more surgical procedures are the risk factors for non-infectious
endophthalmitis post vitrectomy. And it should be remembered in inflammatory cases after surgery in
order to prevent the toxic, irreversible side effects of bacterial endophthalmitis treatment.
8
References
1. Rauen M, Oetting TA, Boldt HC. Two non-infectious forms of endophthalmitis after intravitreal
triamcinolone and cataract extraction. Eye 2009;23:1611-21
2. Couch SM, Bakri SJ. Intravitreal triamcinolone for intraocular inflammation and associated macula
edema. Clin Ophthalmol 2009;3:41-7.
3. Wu L, Velasquez R, Montoya O. Non-infectious endophthalmitis associated with trypan blue use in
cataract surgery. Int Ophthalmol 2008;28:89-93
4. Cheng JW, Wei RL. Ranibizumab for age-related macular degeneration. N Engl J Med 2011;364:582
5. Sun X, Xu X, Zhang X. Counterfeit bevacizumab and endophthalmitis. N Engl J Med 2011;365:378-79
6. Yamashiro K, Tsujikawa A, Miyamoto K. Sterile endophthalmitis after intravitreal injection of
bevacizumab obtained from a single batch. Retina 2010;30:485-90
7. Sharma S, Johnson D, Abouammoh M. Rate of serious adverse effects in a series of bevacizumab and
ranibizumab injections. Can J Ophthalmol 2012;47:275-9
8. Bacon AS ,Davison CR ,Patel BC. Infective endophthalmitis following vitreoretinal surgery. Eye
1993;7:529-34
9. Cohen SM,Flynn Jr HW,Murray TG. Endophthalmitis afger pars plana vitrectomy.Ophthalmology
1995;102:705-12
10. Sharma T, Gopal L ,Therese L. Endophthalmitis in eyes following vitrectomy. Ophthalmic surg lasers
1998;29:857-9
11. Ozdamar A , Aras C , Ozturk R. In vitro antimicrobial activity of silicone oil against endophthalmitis causing agents. Retina 1999;19: 122-6
12. Bartz - Schmidt KU , Bermig J , Kirchhof B. Prognostic factors associated with the visual outcome
after vitrectomy for endophthalmitis. Graefes Arch Clin Exp Ophthalmol 1996;234: 51-8
13. Results of the Endophthalmitis Vitrectomy Study. A randomized trial of immediate vitrectomy and of
intravenous
antibiotics
for
the
treatment
of
postoperative
bacterial
endophthalmitis.
Endophthalmitis Vitrectomy Study Group. Arch Ophthalmol 1995;113:1479-96
14. Han DP, Wisniewski SR, Wilson LA. Spectrum and susceptibilities of microbiologic isolates in the
Endophthalmitis Vitrectomy Study. Am J Ophthalmol 1996;122:1-17
15. Mamalis N, Edelhauser HF, Dawson DG. Toxic anterior segment syndrome. J Cataract Refract Surg
2006;32:324-33
16. Mamalis N. Toxic anterior segment syndrome. J Cataract Refract Surg 2006; 32:181-2
9
17. Moisseiev E, Barak A. Toxic anterior segment syndrome outbreak after vitrectomy and silicone oil
injection. Eur J Ophthalmol 2012 Feb 6:0. doi: 10.5301/ejo.5000116
18. Patnaik B, Biswas C, Patnaik RK. Sterile endophthalmitis in vitrectomised eyes due to suspected heat
resistant endotoxins in the infusion fluid.Indian J Ophthalmol 2004;52:127-31.
19. Smith CA, Khoury JM, Shields SM. Unexpected corneal endothelial cell decompensation after
intraocular surgery with instruments sterilized by plasma gas. Ophthalmology 2000;1107:1561-6
20. Roth DB, Chieh J, Spirn MJ. Noninfectious endophthalmitis associated with intravitreal triamcinolone
injection. Arch Ophthalmol 2003;121:1279-82.
21. Taban M, Singh RP, Chung JY. Sterile endophthalmitis after intravitreal triamcinolone: a possible
association with uveitis. Am J Ophthalmol 2007;144: 50-4.
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Table 1
Clinical characteristics of the patients
No.
Age/
Diagnosis
Surgery
Gender
1
60/M
MH,
Surgery
Endolaser
time (min)
photocoagulation
Cryotherapy
Previous
VA
cornea
AC activtity
treatment
Culture
intraocular
result
(if
surgery
applicable)
Phaco+IOL+C2F6
50
-
-
-
LP
mild edema
Kp(2+),Tyn(3+),hypopyon
PST, TS, IVA
Not done
cataract
2
69/F
RRD
V+SO
80
210
-
Phaco+IOL
HM
clear
Kp(3+),Tyn(3+), hypopyon
PS
Not done
3
30/F
Recurrent
Phaco+V+SO
80
426
-
V
LP
clear
Kp(4+),Tyn(4+), hypopyon
PS
Not done
RD, cataract
4
30/F
VH, PDR
V+SO
80
210
-
-
FC
clear
Kp(4+),Tyn(2+), hypopyon
PS
Not done
5
60/M
Recurrent
V+SO+SB
120
238
-
V+SO
HM
mild edema
Kp(4+),Tyn(2+), hypopyon
PST,OS, IVA
Not done
RD
6
38/F
TRD, PDR
V+C2F6
50
-
-
-
LP
clear
Kp(2+),Tyn(2+),cell(4+)
PS
Not done
7
62/F
VH, BRVO
V+C2F6
10
664
Y
-
HM
clear
Kp(2+),Tyn(2+),cell(4+)
PS
Not done
8
62/F
RRD
V+SO
70
244
Y
-
HM
clear
Kp(3+),Tyn(3+), hypopyon
PS
Not done
9
57/F
VH, PDR
V+SO
90
896
Y
-
HM
clear
Kp(+),Tyn(+),hypopyon
PS, TS
Not done
10
40/F
VH, PDR
V+C2F6
120
972
Y
-
HM
edema
Kp(+),Tyn(3+),hypopyon
TS
Negative
RRD, Rhegmatogenous retinal detachment; IOL, intraocular lens; AC, anterior chamber; KP, keratic precipitates; DM, diabetes mellitus; VH, vitreous hemorrhage; PDR,
proliferative diabetic retinopathy; MH, macular hole; TRD, traction retinal detachment; BRVO: branch retinal vein occlusion; EM, epiretinal membrane; SG, secondary glaucoma;
SO, silicone oil; SB, sclera buckling; V, vitrectomy; PS, periocular steroids; PST, periocular steroids and tobramycin; TS, topical steroids; OS, oral steroids, IVA, intravenous
antibiotics
11
Figure legends
Figure 1. The most series case. (Left) The patient in case 5 presented 1 day post vitrectomy with mild
cornea edema and dense white plaque behind cornea. (Right) Ten days after the treatment of periocular
injection of dexamethasone, oral prednisone and intravenous antibiotics, the clinical appearance had
significantly improved. The cornea was clear and the dense white plaque was completely absorbed.
Figure 2 (Left) The patient in case 9 presented hypopyon with clear cornea 1 day post vitrectomy.
(Middle) The conjunctive was not obvious injection and chemosis. (Right) Seven days after the treatment
of periocular injection of dexamethasone, topical prednisone, the clinical appearance had significantly
improved. The hypopyon was completely absorbed.
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