Acute Onset of Exogenous Endophthalmitis after Dexamethasone Implant Injection Treated without Implant Removal.
As reported in previous prospective randomized trials, dexamethasone intravitreal implant injection (Ozurdex, Allergan Inc, Irvine, CA) has been shown to be an effective treatment option for a variety of pathological conditions, including diabetic macular oedema (DMO), secondary macular oedema (MO) after retinal vein occlusion (RVO), and noninfectious posterior uveitis [1-3]. Long-lasting potency of the implant has been shown to be able to relieve the burden of monthly treatment with anti-vascular endothelial growth factor (anti-VEGF) in resistant cases of MO secondary to diabetes or RVO. The rate of complications with this treatment is low, and the most common side effects are cataract formation in phakic patients and an increase in intraocular pressure (IOP) . Although cases of post-intravitreal injection endophthalmitis are not infrequent , endophthalmitis following dexamethasone implant injection is rare, and few case reports describing this side effect have been published in the literature [6-8]. Because different pharmacological properties can affect infection features, the optimum treatment for post-dexamethasone implant endophthalmitis can differ from the optimum treatments for endophthalmitis from other causes (cataract surgery or intravitreal injection) . In two of the four published cases, the intravitreal implant was removed after vitrectomy, and intravitreal antibiotics (IVABs) were used [6, 7]. In the other two published cases, repeated IVAB injections were used as treatment without vitrectomy or implant removal . To our knowledge, this is the first case report describing endophthalmitis after dexamethasone implant injection managed with 23G vitrectomy without implant removal and followed by administration of IVABs.
2. Case Presentation
A 50-year-old Caucasian woman with no previous ocular pathologies was admitted to our department in 2011 presenting with reduced vision and metamorphopsia in her right eye. Her best corrected visual acuity (BCVA) was 2/10 (6/30) in the right eye and 10/10 (6/6) in the left eye. A clinical examination revealed branch retinal vein occlusion (BRVO) in the inferotemporal vein with secondary MO. Over the course of the subsequent 6 months, anti-VEGF (ranibizumab) treatment was administered, resulting in improved visual acuity without complete resolution of the MO. We then opted to treat the patient with dexamethasone intravitreal implant injection. The procedure was performed in the operating room under topical anaesthesia and sterile conditions. Povidone-iodine periocular scrub and 10% solution were applied to the eyelids, followed by 5% solution to the ocular surface for 3 min. The eye was then draped, and a sterile speculum was used to perform the dexamethasone intravitreal implant injection. After implantation, moxifloxacin 0.5% drops were administered four times daily for 1 week. The patient responded well to the dexamethasone implant and showed BCVA improvement to 9/10 (6/7) and MO resolution lasting for >4 months. Six months after implantation, MO was again present, and BCVA had reduced to 6/9.5. Dexamethasone implant was applied for the second time in the same manner as previously described. On the fourth day after implantation, the patient was admitted to our department with acute pain, redness, and vision loss in her right eye. The right BCVA at that point was 1/20 (6/120). Ophthalmic examination revealed conjunctival injection, mild corneal oedema, grade 3+ anterior chamber cells, hypopyon (1 mm), and an IOP of 8 mmHg. A posterior chamber investigation revealed reduced red reflex and vitreous haze that made observation of retinal detail difficult. The implant was located inferiorly, and fibrous membranes were present in the vitreous cavity with attachment to the retinal tissue. A diagnosis of acute endophthalmitis post implantation was made. On the same evening, a 23G pars plana vitrectomy was performed, and a vitreous tap was acquired at the beginning of the procedure for cultures, sensitivity, and polymerase chain reaction (PCR). We planned to remove the dexamethasone implant using a vitrectome and 23G forceps during the vitrectomy, but this was not possible due to dense membrane formation and low visualisation of the retina at the implantation site. For safety reasons, we opted to leave the implant in place, and at the end of the procedure, we injected vancomycin (1mg/0.1 ml) and amikacin (0.4mg/0.1ml) into the vitreous cavity. Postoperatively, the patient received topical treatment with norfloxacin 0.3% and vancomycin (50 mg/ml) fortified antibiotic drops hourly, atropine drops three times daily, and systemic corticosteroids (8 mg methylprednisolone) daily. Vitreous cultures were positive for Staphylococcus epidermidis, and PCR was negative for Streptococcus spp., Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, Neisseria meningitidis, Streptococcus pneumoniae, and Listeria monocytogenes. The patient responded well to treatment, with a gradual reduction in inflammation and hypopyon as well as an improved vision at 48 h after surgery. One week after treatment, a tapering regimen of drops and steroids was initiated. Three months later, the patient's BCVA was 3/10 (6/19), and a third dexamethasone implantation was performed 6 months after the onset of endophthalmitis, resulting in a BCVA of 8/10 (6/7.5) after 4 months. At the time of writing, 5 years after the onset of endophthalmitis, the patient's VA is 10/10 (6/6, after phacoemulsification) in the right eye, and she requires a dexamethasone implantation once a year.
Currently, the use of intravitreal medications for many different ocular pathologies is common in everyday clinical practice. Endophthalmitis is the most serious complication after intravitreal injection and can significantly impact final visual acuity. The risk of endophthalmitis after intravitreal injection has been reported to range from 0.03% to 1.4% and varies by study and pharmaceutical agent . It is not uncommon for post-intravitreal injection endophthalmitis to be managed similarly to postoperative endophthalmitis [9, 11]. Typically, a vitreous sample is acquired for cultures and PCR, IVABs are administered, and, in severe cases, pars plana therapeutic vitrectomy is performed [4, 9, 11]. In contrast to endophthalmitis after intravitreal injection, post-dexamethasone implant endophthalmitis is rare . Indeed, no cases of acute endophthalmitis were reported in the GENEVA study, and only one case was reported in the MEAD study [1, 2]. Of the cases in the literature describing endophthalmitis after dexamethasone implant injection, two were treated with vitrectomy and implant removal in combination with IVAB administration [6, 7]. In the two other cases, IVABs were administered and repeated after 3 days, and neither vitrectomy nor implant removal was performed . The removal of the implant after vitrectomy is recommended by some clinicians because it is hypothesised that the implant can act as a "depot" for the infective organism and that dexamethasone can deteriorate the immune defence of the host.
In our case as well as in the two cases reported by Esen et al. , the implant maintenance did not result in any additional complications or in a decreased final VA (in all cases, the final VA was better than that at baseline). Further, at 5 years after infection, the VA of the present case is unremarkable when MO is not present. We hypothesise that immediate vitrectomy rapidly reduced the bacterial load in the present case. Moreover, a combined reduction of ocular inflammation related to antibiotics and microorganism products may have occurred due to the action of dexamethasone. The favourable final outcome in this case is likely also related to the cultured bacterium (S. epidermidis), which has been associated with improved prognosis in endophthalmitis patients [9, 11, 12]. Postinjection infections can result from contamination with the commensal flora of patients or surgery staff. Coagulase-negative staphylococci (primarily Staphylococcus epidermidis) and Staphylococcus aureus are found in the conjunctiva and eyelids and on the skin . These, along with oral and nasal commensal flora (primarily streptococci), can spread through droplets [13, 16]. Coagulase-negative staphylococci (primarily Staphylococcus epidermidis), S. aureus, and streptococci have been shown to be common pathogens in postinjection and postcataract endophthalmitis [13,17].
It is possible that the present case of Staphylococcus epidermidis endophthalmitis could have been caused by violation in the injection protocol by any of the surgery staff members. Another possible cause could be the use of contact lenses by the patient the same day she received the injection. It is well known that Staphylococcus epidermidis and other microorganisms can be found attached to the surfaces of contact lenses if proper cleaning, maintenance, and wear habits are not followed [18-20]. In order to prevent similar events in the future, we have reeducated the related surgery staff on safety protocols that must be followed during intraocular injections. We also reminded the patient that contact lenses should be used correctly and safely and should not be used for at least 3 days after injection.
The favourable anatomical and visual outcomes of the present case suggest that challenging cases of endophthalmitis after dexamethasone injection can be effectively treated with immediate pars plana vitrectomy and IVAB administration even without implant removal.
Conflicts of Interest
The authors declare that there are no conflicts of interest regarding the publication of this article.
 D. S. Boyer et al., "Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema," Ophthalmology, vol. 121, no. 10, pp. 1904-1914, 2014.
 J. A. Haller, F. Bandello, R. Belfort Jr. et al., "Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion: twelve-month study results," Ophthalmology, vol. 118, no. 12, pp. 2453-2460, 2011.
 C. Lowder, R. Belfort Jr., S. Lightman et al., "Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis," JAMA Ophtalmology, vol. 129, no. 5, pp. 545-553, 2011.
 J. M. F. Adeniran, D. Jusufbegovic, and S. Schaal, "Common and rare ocular side-effects of the dexamethasone implant," Ocular Immunology and Inflammation, pp. 1-7, 2016.
 D. K. Sigford, S. Reddy, C. Mollineaux, and S. Schaal, "Global reported endophthalmitis risk following intravitreal injections of anti-VEGF: a literature review and analysis," Clinical Ophthalmology, vol. 9, pp. 773-781, 2015.
 M. Arikan Yorgun, M. Mutlu, Y. Toklu, H. B. A. Cakmak, and N. Cagil, "Suspected bacterial endophthalmitis following sustained-release dexamethasone intravitreal implant: a case report," Korean Journal of Ophthalmology, vol. 28, no. 3, pp. 275-277, 2014.
 T. Marchino, J. I. Vela, F. Bassaganyas, S. Sanchez, and J. A. Buil, "Acute-onset endophthalmitis caused by alloiococcus otitidis following a dexamethasone intravitreal implant," Case Reports in Ophthalmology, vol. 4, no. 1, pp. 37-41, 2013.
 E. Esen, S. Sizmaz, and N. Demircan, "Two cases of acute endophthalmitis after intravitreal dexamethasone implant injection," Retinal Cases and Brief Reports, vol. 10, no. 2, pp. 154-156, 2016.
 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," Archives of Ophthalmology, vol. 113, no. 12, pp. 1479-1496, 1995.
 C. A. McCannel, "Meta-analysis of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents: causative organisms and possible prevention strategies," Retina, vol. 31, no. 4, pp. 654-661, 2011.
 M. L. Durand, "Bacterial and fungal endophthalmitis," Clinical Microbiology Reviews, vol. 30, no. 3, pp. 597-613, 2017
 M. L. Durand, "Endophthalmitis," Clinical Microbiology and Infection, vol. 19, no. 3, pp. 227-234, 2013.
 N. E. D. Hoevenaars, D. Gans, T. Missotten, J. Van Rooij, E. Lesaffre, and J. C. Van Meurs, "Suspected bacterial endophthalmitis following intravitreal anti-VEGF injection: Case series and literature review," Ophthalmologica, vol. 228, no. 3, pp. 143-147, 2012.
 T. Grasbon, H. Mino De Kaspar, and V. Klauss, "Coagulase-negative staphylococci of the normal and chronically inflamed conjunctiva," Ophthalmologe, vol. 92, no. 6, pp. 793-801, 1995.
 T. E. Faria e Arantes, R. F. Cavalcanti, M. D. F. Alves Diniz, M. S. Severo, J. L. Neto, and C. M. M. Barbosa de Castro, "Conjunctival bacterial flora and antibiotic resistance pattern in patients undergoing cataract surgery," Arquivos Brasileiros de Oftalmologia, vol. 69, no. 1, pp. 33-36, 2006.
 R. L. Avery, S. J. Bakri, M. S. Blumenkranz et al., "Intravitreal injection technique and monitoring: updated guidelines of an expert panel," Retina, vol. 34, supplement 12, pp. S1-S18, 2014.
 R. C. Gentile et al., "Microbiological spectrum and antibiotic sensitivity in endophthalmitis: a 25-year review," Ophthalmology, vol. 121, no. 8, pp. 1634-1642, 2014.
 L. B. Szczotka-Flynn, E. Pearlman, and M. Ghannoum, "Microbial contamination of contact lenses, lens care solutions, and their accessories: a literature review," Firat Saglik Hizmetleri Dergisi, vol. 36, no. 2, pp. 116-129, 2010.
 S. M. J. Fleiszig, D. J. Evans, M. F. Mowrey-McKee et al., "Factors affecting Staphylococcus epidermidis adhesion to contact lenses," Optometry and Vision Science, vol. 73, no. 9, pp. 590-594, 1996.
 D. Dutta, N. Cole, and M. Willcox, "Factors influencing bacterial adhesion to contact lenses," Molecular Vision, vol. 18, pp. 14-21, 2012.
George G. Bastakis [ID], Anastasios Stavrakakis, Avgoustinakis Nikolaos, Dimitris Dimopoulos [ID], and George Pappas [ID]
Ophthalmology Clinic, Medical Retina & Vitreoretinal Surgery Department, Venizeleio Hospital of Crete, Knossos Avenue 44, Heraklion of Crete, Greece
Correspondence should be addressed to George Pappas; email@example.com
Received 28 June 2018; Revised 27 August 2018; Accepted 17 September 2018; Published 18 November 2018
Academic Editor: Stephen G. Schwartz
|Printer friendly Cite/link Email Feedback|
|Title Annotation:||Case Report|
|Author:||Bastakis, George G.; Stavrakakis, Anastasios; Nikolaos, Avgoustinakis; Dimopoulos, Dimitris; Pappas,|
|Publication:||Case Reports in Ophthalmological Medicine|
|Date:||Jan 1, 2018|
|Previous Article:||A Rare Presentation of Actinic Keratosis Affecting the Tarsal Conjunctiva and Review of the Literature.|
|Next Article:||Radiological-Pathological Correlation in Plasmablastic Lymphoma in an Immunocompromised Patient.|