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ORIGINAL ARTICLE
Year : 2003  |  Volume : 51  |  Issue : 1  |  Page : 39-44

Role of prophylactic intravitreal antibiotics in open globe injuries.


Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Correspondence Address:
S Narang
Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh
India
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Source of Support: None, Conflict of Interest: None


PMID: 12701861

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  Abstract 

Purpose: To determine the efficacy of prophylactic intravitreal antibiotics in reducing the incidence of endophthalmitis after trauma.
Methods: This was a prospective, randomised, case control study of 70 consecutive patients with open globe injury. The patients were prospectively randomised into group I (32 eyes) and group II (38 eyes). Group I patients were given prophylactic intravitreal injection of vancomycin 1 mg and ceftazidime 2.25 mg at the conclusion of primary repair. Group II patients were not given prophylactic intravitreal antibiotics. All the patients received intravenous ciprofloxacin.
Results: The incidence of endophthalmitis was higher in group II (7 of 38 eyes; 18.42%) compared to group I (2 of 32 eyes; 6.25%). Both the patients who developed endophthalmitis despite prophylactic intravitreal antibiotics in group I had an initially undetected intraocular foreign body (eyelash) in the vitreous cavity.
Conclusions: Prophylactic intravitreal broad spectrum antibiotic injection decreases the risk of post-traumatic endophthalmitis.

Keywords: Endophthalmitis, intravitreal antibiotics, prophylaxis, trauma


How to cite this article:
Narang S, Gupta V, Gupta A, Dogra MR, Pandav SS, Das S. Role of prophylactic intravitreal antibiotics in open globe injuries. Indian J Ophthalmol 2003;51:39-44

How to cite this URL:
Narang S, Gupta V, Gupta A, Dogra MR, Pandav SS, Das S. Role of prophylactic intravitreal antibiotics in open globe injuries. Indian J Ophthalmol [serial online] 2003 [cited 2020 Jan 27];51:39-44. Available from: http://www.ijo.in/text.asp?2003/51/1/39/14739



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Endophthalmitis is the most challenging complication of ocular trauma. The reported incidence of post-traumatic endophthalmitis varies from 2.4 to 17% of all open globe injuries. [1],[2],[3] The risk of infection in trauma is significantly high as bacteria inadvertently gain entry into the eye during injury. Culture is positive in 28% and 33% of the eyes of open globe injury from anterior chamber and vitreous tap respectively at the time of primary repair.[4],[5] This justifies the administration of prophylactic antibiotics in cases of open globe injury.[6],[7] However, there are no clear guidelines regarding the use and the route of administration of prophylactic antibiotics. Despite several reports suggesting use of prophylactic antibiotics in cataract surgery, this information cannot be extrapolated to the management of open globe injuries, as the organisms involved and their virulence differ. The use of prophylactic intravenous antibiotics is empirical[6],[7] and is based only on a few experimental studies.[8],[9] Most eye surgeons fear complications associated with the intravitreal injection and their use has therefore been advocated only in high-risk cases of open globe injuries.[10] We carried out a prospective randomised study to determine the efficacy of prophylactic intravitreal antibiotics to reduce the incidence of infection after trauma.


  Materials and Methods Top


This was a prospective, randomised, case control study of 70 consecutive patients with open globe injury who presented to the emergency eye services of our institute between January 1999 and May 2000. The study was approved by the institutional review board. Informed consent was taken from all the patients enrolled in the study and patients could refuse to participate. We excluded eyes with full anterior chamber hyphaema; manifest or suspected endophthalmitis at presentation; and any ocular surgical procedure in the 3 months preceding trauma. We also excluded eyes presenting beyond 72 hours of sustaining injury or if the foreign body removal was delayed beyond one week of open globe injury, since these are established risk factors for post-traumatic endophthalmitis. We also excluded patients with severe ocular trauma from blast and firearm injuries, where it would be difficult to view the intravitreal injection needle in the vitreous cavity. A detailed history was taken in all patients regarding the cause and circumstance of injury. The orbit X-ray was obtained in the postero-anterior and lateral view for all eyes to rule out any retained intraocular foreign body. CT-scan was not done in any of the cases. Preoperative ultrasonography was done wherever indicated. Visual acuity was recorded on Snellen's chart and all the eyes were subjected to slitlamp biomicroscopy and indirect ophthalmoscopy using +90 D and +20 D lens respectively. The extent of wound in terms of zone, type and grade of injury was documented as per the 'Ocular Trauma Classification Group' recommendations. [11] The presence of iris prolapse, lens disruption, vitreous in wound, hyphema and posterior segment complications, if any, were specifically documented. The eye injury was repaired by one of the authors. The findings were reconfirmed intraoperatively under general anaesthesia before starting the repair. Postoperatively, ultrasonography was done as and when required.

The patients were prospectively randomised into two groups by random number tables after obtaining informed consent from the patient or parents in case of minors. Group I patients were given prophylactic intravitreal injection of vancomycin 1 mg and ceftazidime 2.25 mg at the conclusion of primary repair. Intravitreal injection was given 3mm from the limbus in aphakic eyes and 4mm from limbus in phakic eyes. The antibiotics were slowly injected into the vitreous cavity visualising the needle tip. Group II patients did not receive intravitreal antibiotics. However, all patients received intravenous ciprofloxacin (100 mg twice daily) for a minimum of 3 days followed by oral ciprofloxacin (500-mg twice a day) for another 4 days. Anterior segment foreign bodies were removed at the time of primary repair through a separate limbal incision. Eyes with posterior segment foreign bodies received standard 3-port parsplana vitrectomy (PPV) and foreign body removal at the earliest, but always within one week of trauma. Postoperatively, the patients received topical ciprofloxacin 0.3%, betamethasone 0.1%, atropine 1% and oral prednisolone (1mg/kg/day) when required. The severity of intraocular inflammation dictated use of oral corticosteroids. The patients were followed up for a minimum of 3 months (range 3 - 30 months). The incidence of post- traumatic endophthalmitis was compared in the two groups and the risk factors determined applying the 'chi square' test.

For this study, bacterial endophthalmitis was defined as the development of clinical signs including marked anterior segment inflammatory reaction, hypopyon, vitritis including vitreous exudates, purulent discharge from the wound, gas bubbles, and retinal vasculitis with or without culture positivity. These patients received pars plana vitrectomy and intravitreal injection of vancomycin (1mg) and ceftazidime (2.25mg). Before starting the infusion line, an undiluted vitreous sample was aspirated from the mid-vitreous cavity with the help of 2 c.c disposable syringe connected to the suction tubing of a vitreous cutter. The vitreous aspirate was sent for microbiological investigations including gram stain, KOH 10% and calcoflour 1% smear and bacterial and fungal cultures. For cultures, vitreous samples were divided into two portions. One portion was transported to the microbiology laboratory in Robertson cooked meat media for bacterial cultures. The samples were inoculated into sheep blood Columbia agar base (High - Media), chocolate agar Columbia agar base and MacConkey's agar media at 37°C. The second portion was directly inoculated on two plates of Sabaraud's dextrose agar (SDA) media under fully sterile conditions and inoculated at 25°C and 37°C in the laboratory for a minimum of 6 weeks for fungal cultures. Postoperatively, if the smears were KOH negative, the patients received intravenous ciprofloxacin (100mg twice daily) and oral prednisolone (1mg/kg body weight/day) in addition to the topical medication. If the smears and/or cultures were positive for fungi, intravitreal amphotericin B (5 µg) was administered and oral itraconazole 100 mg twice daily was added for minimum of 6 weeks with tests for adequate liver functions. In fungus-positive cases oral prednisolone was reduced to 0.5 mg/kg/day under the cover of oral antifungal agents. Intravenous and intravitreal antibiotics were changed according to sensitivity results if the endophthalmitis did not respond to the initial treatment.


  Results Top


The study included 70 eyes of 57 males and 13 females. The age ranged from 2- 62 years (median 22 years). Of the 70 eyes, 32 were randomised into group I and 38 into group II. The interval between injury and repair varied from 1-3 days; 44 eyes were repaired within 24 hours of injury, 20 eyes in 24- 48 hours and 6 eyes were repaired 48-72 hours after injury [Table - 1]. The cause of trauma was sports related in 26 (37.1%) eyes, traffic accidents in 14 (20%), occupational injuries in 14 (20%) and miscellaneous causes in 16 (22.9%) eyes. Of the 70 eyes, 59 eyes (84.29%) sustained injury in rural (28 eyes in group I and 31 eyes in group II) and 11 (6.36%) in urban environment (4 in group I and 7 in group ll) [Table - 1]. History of sharp penetrating injury (type B or type C) was present in 61 (87.14%) eyes (29 and 32 in group I and group II respectively). Type A injury i.e. globe rupture was seen in 9 eyes (3 and 6 in group I and II respectively). Intraocular foreign body was present in 16 eyes (8 in each group). At the time of initial presentation, intraocular foreign body was clearly visualised in the anterior chamber in 4 eyes and visualised as radio-opaque shadow in X-ray in 10 eyes that were also localised ultrasonographically in the posterior segment. In two eyes, neither X-ray nor ultrasonography could diagnose any intraocular foreign body. Later they were found to be eye lashes at the time of parsplana vitrectomy for endophthalmitis.

Of the 70 eyes, 13 (18.57%) eyes had posterior extent of laceration extending beyond the ora serrata i.e. Zone 3. Zone 1 and 2 injury was seen in 29 and 28 eyes respectively. Both the groups were balanced and comparable (p>0.05) with respect to the known risk factors for endophthalmitis such as the cause and circumstance of injury, presence of intraocular foreign body and the extent of injury [Table - 2][Table - 3]. The incidence of hyphaema, lens disruption, iris prolapse, vitreous haemorrhage, and vitreous prolapse was comparable (p>0.05) in the two groups [Table - 3]. Retinal detachment was detected in 6 eyes (2 eyes in group I, 4 eyes in group II) in the first postoperative week. Of these, two were associated with posterior perforation and two with the presence of intraocular foreign body. Standard 3-port pars plana vitrectomy with internal tamponade [perfluoropropane (C 3 F 8 ) gas in two eyes and silicone oil in two eyes] with scleral buckle was done in 4 eyes, scleral buckling alone in one eye and one eye was considered inoperable because of poor visibility secondary to extensive corneal damage. Haemorrhagic choroidal detachment was present in two eyes (1 in each group). At the time of primary repair, lens matter aspiration was done in 12 eyes (6 in each group), and hyphaema drainage in 2 eyes (1 in each group). Pars plana vitrectomy was carried out for all the eyes that developed endophthalmitis during follow-up and also for certain other indications as and when required [Table - 4]. In 4 eyes the intraocular foreign body (IOFB) was removed through limbus at the time of primary repair (one in group I and 3 in Group II) and removal of foreign body after pars plana vitrectomy was done in 10 eyes (5 in each group) within one week of injury. Two eyes in group I had undetected IOFB (eyelashes in vitreous cavity) that became apparent only when they developed endophthalmitis and hence needed vitrectomy 3 and 4 weeks after sustaining injury.

Endophthalmitis developed in 9 (12.9%) eyes. The incidence of endophthalmitis was higher in group II (7 eyes; 18.42%) compared to group I (2 eyes; 6.25%). This difference was not satistically significant. Both eyes that developed endophthalmitis in group I despite prophylactic intravitreal antibiotics, had an eyelash in the vitreous cavity and was neither suspected nor deleted earlier. If we exclude the two eyes with undetectable foreign body, the incidence of endophthalmitis was significantly less in group I as compared to group II (0% versus 18.42%; P = 0.03).

All the 7 patients in group II developed endophthalmitis within 12 days (mean 7 days) after trauma and presented as hypopyon, fibrinous reaction in anterior chamber, dense vitreous exudates and retinal abscesses. All the eyes that developed endophthalmitis belonged to type B or type C (penetrating eye injuries) open globe injuries. Of the 7 eyes that developed endophthalmitis in group II, only one eye had a wound extending beyond ora serrata (zone 3); and two had intravitreal foreign body. Other signs included hyphaema (n = 3), lens disruption (n = 3), iris prolapse (n = 5), vitreous into the wound (n = 2), vitreous haemorrhage (n = 3) and choroidal detachment (n = 2) [Table - 5]. Of the 9 cases with endophthalmitis 8 had sustained trauma in rural settings. The cultures were positive in 5 of the 9 endophthalmitis eyes and grew Staphylococcus epidermis in 3 eyes, Staphylococcus aureus in one eye and Aspergillus flavus in one eye. The bacteria were sensitive to ciprofloxacin and vancomycin. None of the eyes in group I developed any complication attributable to the intravitreal injection.

The final visual acuity of > 3/60 was achieved in 52 (74.29%) eyes (24 in group I and 28 in group II) and of these, visual acuity of > 6/ 12 was seen in 15 (21.43%) eyes (7 in group I and 8 in group II). Visual acuity of < 3/60 was seen in 16 (22.86%) eyes ( 6 in group I and 10 in group II). Two patients in group I did not cooperate for visual acuity testing though they had good light fixation. In the 9 eyes that developed endophthalmitis, the final visual acuity ranged from 6/24 to no light perception. Two eyes in group ll were phthisical at the end of the follow-up [Table - 4].


  Discussion Top


The incidence of post-traumatic endophthalmitis varies from 2.4 - 17% of all open globe injuries. [1],[2],[3] The figures double and approach 30% in rural settings.[2] This high incidence of post-traumatic endophthalmitis warrants the use of stronger prophylactic measures. Further, the endophthalmitis following penetrating eye injuries has a relatively poor prognosis because of the delayed diagnosis, infection by more virulent and resistant organisms, and polymicrobial infections.[2],[12] Despite poor prognosis and high incidence of post-traumatic endophthalmitis, the use of prophylactic antibiotics and their route of administration in open globe injury is controversial.[10] The use of prophylactic intravenous antibiotics has been recommended by many authors on the basis of experimental trials which showed that intravenous antibiotics achieve adequate intravitreal concentration in traumatised eyes. [6],[7],[8],[9],[13],[14],[15],[16],[17],[18]There are however no human clinical studies to support the efficacy of this recommendation because of the substantial logistic problems that accompany such a trial. The third generation cephalosporins, ceftriaxone, and ceftazidime, when given intravenously and 4-flouroquinolones given orally or intravenously demonstrate therapeutic intravitreal concentrations and have therapeutic efficacy against commonly infecting organisms.[11],[19],[20],[21],[22] The commonly involved gram-positive pathogens in post-traumatic infections are Staphylococcus and Bacillus species while Pseudomonas remains the most important gram-negative pathogen.[23],[24] The mean drug concentration of oral and topical ciprofloxacin in the aqueous (14.43 + 6.9mg/mL) and vitreous (1.98 + 1.2mg/mL) of traumatised eyes exceeds the MIC 90 (0.5mg/mL -2mg/mL) of most of the above microorganisms.[16],[17] It has been shown that 93-100% of all organisms causing post-traumatic endophthalmitis are susceptible to ciprofloxacin.[24] However, the major problem is the development of resistance of organisms against ciprofloxacin.

Traumatic endophthalmitis developed in 18.42% of eyes in group II in our study despite use of prophylactic intravenous ciprofloxacin. Vancomycin has become the treatment of choice for resistant infections.[25] The susceptibility of pathogens in post-traumatic endophthalmitis to vancomycin varies from 80 to 100%.[24] The ocular penetration of vancomycin in eyes with intact vitreous is poor.[13] We used a combination of intravitreal vancomycin and ceftazidime, which is effective against most gram-positive and gram-negative organisms including Bacillus .[26],[27] The use of prophylactic intravitreal antibiotics at the time of primary repair has been recommended earlier in high-risk cases.[6],[10] The major feared complications associated with intravitreal injection are vitreous haemorrhage, retinal hole/break, retinal detachment, choroidal haemorrhage and cataract. The complications can be avoided by giving the injection slowly and only after visualising the needle tip in the vitreous cavity. We did not encounter any of the complications due to intravitreal injection.

The incidence of post-traumatic endophthalmitis was lower in the group subjected to intravitreal antibiotics. The eyes that developed endophthalmitis in group I despite prophylactic intravitreal antibiotics had an eyelash in the vitreous cavity that was initially undetectable, clinically or on ultrasonography, and was first detected 3-4 weeks after trauma at the time of vitreous surgery for endophthalmitis. The intraocular foreign body could not be removed within 1 week of sustaining trauma as defined in the protocol of the study. If we exclude the eyes with undetectable foreign bodies, the use of intravitreal antibiotic prophylaxis in group I significantly lowered the incidence of endophthalmitis as compared to group II that did not receive prophylactic intravitreal antibiotics (0/30 vs 7/38; p = 0.03). Intravitreal vancomycin and ceftazidime were effective as prophylactic therapy against post-traumatic endophthalmitis if the eye did not harbour a foreign body. In our series, the benefits of the prophylactic intravitreal injection outweighed the potential risks.

Earlier studies have shown that delayed repair, lens disruption, size of corneal laceration, intraocular foreign body and posterior segment trauma are the risk factors in development of endophthalmitis.[1],[6],[28] In the present study however, posttraumatic endophthalmitis was not associated with iris prolapse, lens disruption, intraocular foreign body, vitreous haemorrhage, and vitreous prolapse if the injuries were repaired early and the foreign body removed at the earliest.

To conclude, prophylactic intravitreal antibiotics seem to prevent severe intraocular infection following open globe injury. This should be included as a standard of care.

 
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Pieramici DJ, Sternberg P, Aaberg TM , Bridges WZ, Capone A, Cardillo JA, et al. The ocular trauma classification group. A system of classifying mechanical injuries of the eye (globe). Am J Ophthalmol 1997;123:820-31.  Back to cited text no. 11
    
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Meredith TA, Aguilar HE, Shaarawy A, Kincaid M, Dick J, Neisman MR. Vancomycin levels in vitreous cavity after intravenous administration. Am J Ophthalmol 1995;119:774-78.  Back to cited text no. 13
    
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Hanioglu-Kargi S, Basci N, Soysal H, Bozkurt A, Gursel E, Kalyaap O. The penetration of ofloxacin into human aqueous humor given by various routes. Eur J Ophthalmol 1998;8:33-36.  Back to cited text no. 14
    
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Ozturk F, Kortunay S, Kurt E, Icher SS, Basci NE, Bozkurt A. Penetration of oral and topical ciprofloxacin into the aqueous and vitreous humor in inflamed eyes. Retina 1999;19:218-22.  Back to cited text no. 16
    
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    Tables

  [Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5]


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