The serious eye inflammation of post intraocular Avastin injection

Retrospective statistical study a collection of all patients with post intra vitreal injection (IVI) endophthalmitis in last 10 year period between 2010–2019 in eye department of Tobruk medical center -Tobruk and eye department of Alwahda hospital Derna. We aim in this study to review the microbiology, clinical characteristics, diagnosis, and management strategies of post-intra vitreal injection endophthalmitis, by comparing our results with the different studies designs and treatment protocols. There were 9 patients of the after intra vitreal injections endophthalmitis cases. The age average is 70 years, 6 cases are females and 3 casees are male, all of them were practice post intravitreal Avastin injection endophthalmitis. There were 8 patients had Diabetes mellitus (DM), 2 patients had cardiovascular disease and 1 patient had hepatitis C as a systemic disease. The most common causative organism after intra vitreous injection endophthalmitis is Coagulase-negative staphylococci (CNS) 100% from the 56% positive causative organisms and 44% are no detected microorganisms, the outcome of cases which managed with pars-plana-vitrectomy (PPV) improved significantly about 60 Letters (> 3 Lines) and cases managed without PPV > 15 Letters (> 3 Lines). The cases of post intraocular endophthalmitis which diagnosed and treated early with PPV give a good result and can save the vision. The cases of acute POE in the first 3 day had significant better function (P value = 0.02).


Introduction
Endophthalmitis is a severe intraocular inflammation, due to bacterial or fungal infection, including involvement of the vitreous and/or aqueous humors. It can causes permanent damage to retinal photoreceptors that may lead to partial or complete loss of vision, even with intensive medical and surgical management. For that reason, endophthalmitis is an emergency condition. Endophthalmitis can be caused by either exogenous (micro-organisms diffuse inside the eye through surgery or trauma) or endogenous (through blood from inside the body, through infection or sepsis), [Callegan, Engelbert, Parke and Gilmore 2002].
The post intraocular injection is a rare postoperative endophthalmitis. This is 0.03%-0.072% of all cases of anti-endothelial vascular growth factor (VEGF) injection [Hoevenaars et al.,  After the introduction of bacteria into the posterior segment, endophthalmitis follows one of two following paths: mild inflammation with effective treatment, which lead recovery of infection, or severe inflammation, not controlled with treatment, which lead to vision loss. [Callegan, Engelbert, Parke and Gilmore 2002].
The most common causes of endophthalmitis are from the patient's conjunctival flora, contamination of sterilised instruments, disposable Most patients with post-operative endophthalmitis complain from pain and visual loss, and present with signs of conjunctival injection, fibrinous exudation, hypopyon and vitritis. [Rudnisky, Wan, et al. 2013] There are some methods in management of postoperative endophthalmitis, including prophylaxis, medical and surgical. There are four methods to confirm the diagnosis; [1] taking aqueous samples and vitreous samples. [2] conjunctival swabs [3]  Topical antibiotics; which are used to protect the wound from infection but have limited benefit [Lundström, Wejde, et al. 2007]. Topical dexamethasone; which can be used initially 2-hourly in the severe cases. Topical mydriatic; which can be used twice daily.

Archives of Medical Case Reports and Case Study
Systemic medication: Systemic antibiotics: although some studies suggested systemic antibiotic treatment had no effect on the course and outcome of endophthalmitis, however, most recent retrospective still advise to use two types of broad spectrum systemic antibiotics to cover both gram positive and gram-negative organisms, the most commonly used antibiotics, for example: vancomycin 2x 1g i.v. to cover grampositive organisms, and a third-generation cephalosporin (ceftazidime) 3x 2g i.v. to cover gram-negative organisms, [Novosad and Callegan 2011, Bertino, 2009]. In case of alternative clindamycin 3x 600 mg oral plus ciprofloxacin 2x 750 mg oral or 3x 400 mg i.v. [Behrens-Baumann, Frank, 2010].
Systemic steroid must be used in severe cases of endophthalmitis to limit the destructive complications of the inflammatory process, but should excluding fungal infections.
Intravitreal antibiotics and steroids: [Silver standard]; An intra-vitreal injection of antibiotic should be immediately given to decrease the concentration of most organisms and quickly sterilize the eye.

Materials and Methods
Retrospective study done through collection of the data from the Statistic office in Tobruk medical center-Tobruk and Alwahda hospital-Derna. The recorded data included clinical features of the most serious complication (endophthalmitis) of the post intra vitreal Avastin injection; the data was collected are visual acuity at diagnosis, age and sex of the patients, time of the disease, type, type of management. Additionally classified were operations protocol, type of organism that caused the disease, lab findings , systemic and local disease of affected patients, and the outcome for the patient through the VA findings. We depend on Ranges of vision loss and reading performance (Tab. No. 1) to a get the result of improvement of vision cases of post intraocular Avastin injection endophthalmitis (improvement of vision > 3 lines i.e > 15 letters on visual chart considered clinically a significant improvement). Statistical analysis was performed using Microsoft Office Excel program. Nominal and statistical significant variables were analysed using t-test for two samples. P value ≤ 0.05 or level (95%) was considered statistically significant.  Table. ICD 9 Ranges of vision loss and reading performance ** modefide Table. Recomindation of the DOG to quality assurance of neurophysiological tests and advice version-11

Results
Out of the 9 recorded patients of intravitreal injections endophthalmitis cases, there were 8 patients which receive the medication for treatment of diabetic macular edema, one case for treatment of age related macular degeneration AMD. The age average is 70 years, 6 cases were females and 3 cases were male, all of them were practice postoperative endophthalmitis. There were 8 patients had DM, 2 patients had heart disease and 1 patient had hepatitis C as a systemic disease.
There were 8 cases (89%) where complain from pain, redness and blurred of the vision and one case were pain non remarkable. There were 5 cases presented with synechia and hypopion in the anterior chamber and 4 cases without hypopion, all of the cases were with cells in anterior chamber and vitreous. All the cases after intravitreal medication injections where is acute i.e. the endophthalmitis occurs < 28 days, the most is in the first 10 days, and there are (66.7%) of cases occurs at first 3 days.

*Ranges (ICD-9-CM)
Decimal VA The most common causative organism after intra vitreous injection endophthalmitis is Coagulase-negative staphylococci (CNS) (100%) from the 56% positive causative organisms and 44% are no detected microorganisms, see the Figure   Figure1: causative organisms of post intravitreous injection endophthalmitis: There were 6 patients (66.7%) from all cases of after intravitreal injection were presented with near Blindness vision and two cases with sever blurred of vision and one case with mild blurred of vision. There were 7 patients managed with PPV + intra vitreous medication injection with washing the anterior chamber. The Log MAR Loss of Vision average at diagnosis is 1.98 and at discharge (after receive their management) is 1.3, the vision improved significantly after the management about 30 Letters i.e. improved (> 6 Lines). Although the cases which managed with PPV had worser visual acuity at time of diagnosis Log MAR 2.1 they had clinically better outcome after the management Log MAR 1.5 than the cases which managed without PPV (Log MAR at diagnosis 1.7 and 1.3 after the management), i.e. the outcome of cases of PPV improved significantly about 60 Letters (> 10 Lines) and cases managed without PPV >15 Letters (> 3 Lines).

Discussion
Avastin is anti-vascular endothelial growth factor (anti-VEGF), these therapy has improved the quality of life for many patients with diabetic maculopathy, age-related macular degeneration, and other ocular diseases involving neovascularization and retinal edema. In these pathologies, the inhibition of intraocular VEGF is the only therapy that can preserve vision. [Semeraro et al., 2015]. Chan, 2012, which advised immediately PPV make a significant outcome improvement cases of postoperative endophthalmitis, there were 7 patients managed with PPV + intra vitreous medication injection with washing the anterior chamber, the vision improved significantly after the management about 30 Letters i.e. improved (> 3 Lines). Although the cases which managed with PPV had worser visual acuity at time of diagnosis they had clinically better outcome after the management than the cases which managed without PPV, i.e. the outcome of cases of PPV improved significantly about (> 10 Lines) and cases managed without PPV Letters (> 3 Lines).

Conclusion
Although the postoperative endophthalmitis is sight threatening infection and destructive emergency disease, the appropriate prophylaxis is remain the best way of infection prevention. The delayed presentation, inappropriate management procedures, and severity of causative organism may account for the unfavorable visual outcome. In general post intravitreal endophthalmitis cases can be treatable condition especially when had diagnosed and managed early time with intravitreal antibiotics and early pars-plana-vitrectomy. Statistically we consist, the cases of acute intravitreal endophthalmitis in the first 3 day had significant better function outcome (P value = 0.024).