Silicone Oil in Surgical Management of Endophthalmitis: History
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Contributor:
Fabrizio Sinisi
,
Marco Della Santina
,
Pasquale Loiudice
,
Michele Figus
,
Giamberto Casini

Endophthalmitis represents one of the biggest diagnostic and therapeutic challenges in modern ophthalmology. It threatens all forms of intraocular surgery from intravitreal injections to corneal transplants and vitrectomies and it is discussed on all surgical consent forms. Silicone oil reduces the risk of postoperative retinal detachment, especially in case of undetected retinal breaks, produces compartmentalization of the eye, may lead to early visual recovery, allows laser photocoagulation, prevents severe postoperative hypotony and has antimicrobic activity due to an inhibitory effect for several species of pathogens. 

  • endophthalmitis
  • pars plana vitrectomy
  • silicone oil

1. Introduction

Endophthalmitis is an inflammatory process involving the internal structures of the eye mainly caused by exogenous agents such as bacteria, mycetes and occasionally parasites which may penetrate the eye in the intraoperative or postoperative phase, after eye injuries or may spread from ocular surface infections.
Postoperative endophthalmitis can be classified as acute, whether the infection is developed within 6 weeks from the intraocular procedure, or chronic.
Rarely, in endogenous endophthalmitis, the infectious agent reaches the eye through the bloodstream; this usually occurs in patients with risk factors such as immunosuppression or intravenous drug abuse.
Endophthalmitis is usually defined by severe inflammation of the ocular tissues and fluids characterized clinically by a combination of signs and symptoms including ocular pain, decreased vision, eyelid oedema, conjunctival congestion, chemosis, anterior segment inflammation, hypopyon, vitritis, and decreased red reflex.

2. Epidemiology and Causative Agents

The incidence of postoperative endophthalmitis has sensibly decreased over the years. Most cases of endophthalmitis are exogenous, and organisms are introduced into the eye via trauma, surgery, or ocular surface infections. Endogenous endophthalmitis occurs when the eye is seeded via the bloodstream [1].
The rate of occurrence ranges between 0.13% and 0.7% following cataract surgery [2][3][4] and between 0.03 and 0.13% after PPV [5]. The large diffusion of intravitreal injections has drastically increased the volume of intraocular procedures in the population, with the result of performing some of these outside the operating room setting [6]. Nevertheless, recent studies reported a relatively low rate of post-injection infections ranging between 0.02% and 0.082% [7][8][9][10][11][12].
Post-traumatic endophthalmitis accounts for 25–31% of cases and the reported incidence rate of endophthalmitis following open-globe injury varied from 0% to 16.5% with evidence of reduction over the past 70 years [13].
Depending on the causative agent, two main categories are recognized: bacterial and fungal endophthalmitis. The predominant organism causing the infection depends on the source (vegetable matter or retained intraocular foreign body), route of spread (post-surgery, trauma, delayed onset or hematogenous dissemination), geographic location, and patient characteristics [14]. Among exogenous endophthalmitis, Gentile and coscholars observed that 85.1% were due to gram-positive bacteria, 10.3% were due to gram-negative bacteria, and 4.6% were due to fungi. The most common bacterial pathogens isolated are Staphylococcus epidermidis (30.3%), different species of coagulase-negative Staphylococcus (9.1%), Streptococcus viridans (12.1%), Staphylococcus aureus (11.1%), Enterobacteriaceae (3.4%), and Pseudomonas aeruginosa (2.5%) [15].

3. Therapy

The key points in endophthalmitis treatment are infection control and eradication, inflammation management and re-infection prevention.

3.1. Medical Therapy

Systemic antibiotics in postoperative endophthalmitis are adopted as adjuvant therapy in some units despite little published evidence on their clinical efficacy [16]. As early as 1995, the EVS study concluded that a systemic treatment with ceftazidime 2 g every 8 h, amikacin 7.5 mg/kg initial dose followed by 6 mg/kg every 12 h did not affect the final visual outcome. Moreover, the scholars hypothesized that the omission of systemic antibiotic therapy could reduce toxic effects, costs and length of hospital stay [17]. However, given the lack of univocal guidelines, adjunctive systemic antibiotic therapy is still commonly used resulting in various antibiotic regimens. The best-documented systemic drugs achieving therapeutic levels in vitreous appear to be fourth-generation fluoroquinolones [18], meropenem, and linezolid [19]. Conversely, patients with endogenous endophthalmitis seem to benefit from combined intravitreal and systemic antimicrobial therapy with lower rates of evisceration or enucleation [20].
Broad-spectrum antibiotic combinations are usually started before a specific pathogen is identified and antibiotic sensitivity is determined. One of the drugs should be effective against Gram-positive organisms and the other one against Gram-negative organisms. Once antibiotic sensitivity is determined, targeted intervention should be undertaken. In the presence of corneal ulcer or wound abscess, fortified drops (including cefazolin 5%, tobramycin 1.4% and Vancomycin) should be used.
Intravitreal antibiotics are a mainstay for the management of endophthalmitis. The intravitreal route represents the only way the highest safe level of antibiotic can be rapidly delivered in the vitreous chamber. An early injection is crucial because pathogens continue to replicate over time, produce toxins and dramatically damage the surrounding environment leading to irreversible visual loss. High doses of antibiotics are needed to keep their levels above the bacterial minimal inhibitory concentration as long as possible, given the variable speed of antibiotic clearance depending on the surgical and inflammatory status of the eye. In vitrectomized eyes, if on one hand there is a higher risk of transient neurotoxicity due to macular pooling of the drug after injection, on the other hand, the absence of the vitreous body entails a quicker antibiotic clearance and drug concentration may sooner decrease to subtherapeutic levels [21].

3.2. Surgical Therapy

The EVS concluded that early vitrectomy in endophthalmitis was only beneficial to patients with vision of light perception or worse; however, this was a secondary finding as the study had not been designed for such subgroup analysis. Already in 2005 Kuhn and Gini questioned the EVS indications on vitrectomy showing their results in a case series of 47 patients who had undergone early vitrectomy for endophthalmitis, with a ‘complete’ surgical vitrectomy as opposed to “core”: 91% of the cases achieved final acuity of 20/40 or better, as opposed to 53% in the EVS group [22]. The authors suggested that removing the posterior vitreous was advantageous in clearing the toxic load away from the macula whereas the EVS approach may have led to ‘macular hypopyon’, resulting in long-term dysfunction. In recent years, with increased experience and surgical technique refinement, a more proactive stance in favour of vitrectomy has been adopted by many surgeons, outdating the EVS indications [16].

4. Antimicrobial Activity of Silicon Oil

Among SO properties, antimicrobial activity has been extensively investigated. It has been suggested that the high surface tension and low permeability of SO could limit the freedom of movement of the pathogens, concentrating them in the ciliary body or close to the retinal blood vessels where the defence mechanisms could act more effectively [23]. Moreover, the space-occupying action of a long-standing tamponade may play an important role in pathogens’ and toxins’ wash-out, preventing the damage of the delicate retinal structures [24][25].

The in vitro antimicrobial activity of SO against anaerobic agents, specifically Propionibacterium acnes, Peptostreptococcus spp., Peptostreptococcus anaerobius, Bacteroides fragilis, Fusobacterium spp., and Clostridium tertium has been investigated [26]. After a prolonged incubation of 7 days, 9.2 × 106 colonies were observed in the silicone oil for Propionibacterium acnes, which may have been due to its biofilm formation capabilities. Additionally, Propionibacterium acnes produces propionic acid as a metabolic product, and the chemical effect of propionic acid on SO is not known. This chemical interaction may have contributed to the retention of bacterial viability in the SO [26].

Another evidence of biofilm-producing capabilities causing SO resistance has been reported in a case of endophthalmitis following retinal detachment surgery with SO injection at the end of the procedure. M. abscessus, a notorious organism, was isolated after gene sequencing; it tends to form a biofilm, hence becoming highly resistant to antibiotics. In this case, the antibiogram sensitivity chart showed sensitivity only to piperacillin-tazobactam [27].
Finally, SO seems to lack effectiveness against Fusarium spp., the most frequently isolated fungus after Aspergillum. In these cases, a central vitrectomy may be preferred to a complete one due to lower visibility and consequently higher risk of iatrogenic damage. SO tamponade is not recommended given the absence of proven fungicidal activity, moreover, antimycotic drug concentration may change in silicone oil [28][29].
In cases of fungal endophthalmitis associated with retinal detachment, it could be appropriate to perform retinal detachment surgery as soon as the infection resolves [30].

5. Anatomical and Visual Outcomes

Back in 2009, SO injection after complete PPV proved to lead to earlier infection control, better anatomical and visual outcomes, and a lower re-intervention rate in comparison with only intravitreal antibiotic injection [31]. In 2012 Patel et al. confronted the results obtained in 129 endophthalmitis patients treated with and without SO injection PPV in a prospective randomized clinical trial. The use of SO was related to better anatomical outcomes and a reduced number of reinterventions, the latter related to better visual outcomes. These results were even better in the post-traumatic endophthalmitis subgroup. 

The protective action exerted by SO has been confirmed in eyes at high risk for infections: the 2-year cumulative incidence of endophthalmitis was 31.2% in patients who received Boston Type 1 keratoprosthesis alone versus 0% in the group who received PPV and SO injection [32].

6. Retinal Detachment and Endophthalmitis

A retrospective case series of patients suffering from endophthalmitis, and retinal detachment treated with PPV and SO injection analyzed anatomical and visual outcomes among two groups. Group 1 included patients with concurrent endophthalmitis and retinal detachment, Group 2 included patients with delayed onset retinal detachment. The retinal reattachment rate was higher in the delayed onset group; however, the final visual outcome did not show statistically significant differences. SO was effective in the management of retinal detachment related to endophthalmitis although low visual outcomes are likely to be expected [33].

Farouk and colleagues observed better infection control and lower postoperative retinal detachment rates in post-cataract endophthalmitis patients treated with PPV and SO injection [34]. Although postoperative visual acuity was not significantly better in eyes treated with SO injection, in a subgroup analysis, the number of patients with worsened visual acuity after the intervention was lower in the SO group. Therefore, SO may play a role in preventing visual deterioration [34].

7. Limitation of Silicone Oil Use

Performing a complete vitrectomy before SO injection is not always possible in eyes with severe endophthalmitis; firm adherence of inflammatory debris to the retina and fundus visualization problems due to corneal oedema and pupil membranes may complicate the surgical procedures. Moreover, the use of SO during the surgical treatment of endophthalmitis has some disadvantages, including the retinotoxic potential and the observation that not all pathogens are inhibited by this substance.
SO low-molecular weight compounds may diffuse out of the vitreous cavity, resulting in retinal toxicity and affecting eye physiology by absorption of lipophilic molecules from the ocular environment [35].
Vitreous humor plays a crucial role in eye physiology and must not be considered an inert optical medium; it is central in intravitreal pharmacodynamics and its buffering capacities have been demonstrated [36].
Replacement of vitreous humor with SO may interfere with toxin washout. Several defence mechanisms within the retina such as the blood-retinal barrier, cytochrome p450 activity and antioxidants protect the retina against a variety of insults. Since the waste products of the retina diffuse into the vitreous, the effective volume of the vitreous space is also important in detoxification as the amount of this space is inversely related to the concentration of toxic materials. Therefore, with the reduction of effective vitreous space, the tolerable number of acids or toxins is likely to be reduced. In the context of endophthalmitis with a high retinal metabolic rate, increased production of waste products, and acidification of the retinal environment, replacing vitreous with SO may expose the retina to more rapid decompensation and damage [37].
Dosing intravitreal antibiotics in SO-filled eyes can be challenging. The physician will struggle both with lower retinal toxicity thresholds and with a higher antibiotic clearance; the medication becomes more dangerous and stays in the vitreous chamber for less time [38].
SO causes compartmentalization in the eye that may trap inflammatory debris between the SO and retina, leading to the development of pre-retinal membranes that could cause retinal tears. The presence of SO and consequent compartmentalization may also influence the distributions of intravitreal antibiotics that can reach toxic concentrations. In addition, the toxicity of SO for the optic disc should be seriously considered [39].

This entry is adapted from the peer-reviewed paper 10.3390/jcm11185445

References

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