EVRS EDITORIAL

Facing Endophthalmitis

A European perspective on the EVS study.

GIAMPAOLO GINI, MD

You have finished a day's work in the operating room. You may be tired, but you are happy with yourself. You feel your surgery has done your patients a considerable amount of good, and, as you drive home, you smile, anticipating the gratification you will receive as your patients glide through your reading chart the following day.

Unfortunately, it only takes a little bug to upset this blissful scenario. Surgeons occasionally take holidays, but germs do not.

One of the most frustrating feelings I have experienced during my years as an ophthalmic surgeon has been the onset of postoperative endophthalmitis. Actually, I should not be using the past tense because, like anyone else, I still do get my occasional infection despite all the efforts aimed at preventing it

So, what do we know today that can help us prevent postop endophthalmitis and improve its prognosis when it does occur? These are the questions we will try to answer in this column.

TEACHINGS FROM THE PAST

Endophthalmitis that results from any invasive procedure on the eye is an unpredictable event that can either present as a cluster of several cases grouped together or as an isolated, sporadic event.

In the former instance, the adverse event is somehow related to the materials and procedures that revolve around the surgical process itself. What this amounts to is that there is something wrong in your operating room, and all the procedures aimed at preventing contamination should be reviewed before any further surgery is carried out.

In the latter case, it is very likely that the contaminating agent was harbored by the host and became aggressive only after having entered the eye.

Many authors and multicenter studies have contributed a great wealth of data to our understanding of the role that saprophythic bacteria, either present in the conjunctival fornix or on the lid margin, play in determining whether postop endophthalmitis will occur. Thus, we ophthalmic surgeons have, from time to time, revisited a concept that has always been very clear to our general surgery colleagues: the thorough disinfection of the operating field. Along with careful disinfection of the skin and lid margins, as well as accurate draping, it has become common practice to instill polyvinyl alcohol-iodine or povidone-iodine in the conjunctival fornix several minutes before any invasive procedure is carried out on the eye. Some clinicians also advocate the use of a brief preoperative cycle of topical antibiotics.

However, as any biologist will tell you, complete eradication of all bacterial colonies preoperatively is virtually impossible. Special care should therefore be used in identifying those individuals that may have a less efficient immune response. These patients need stricter postop surveillance and may occasionally benefit from the use of antibiotics in the infusion liquids. It is beyond the scope of the present discussion to judge whether the routine use of antibiotics in the infusion liquids is an ethically acceptable practice. It is my belief that, although this is undoubtedly helpful in preventing the onset of endophthalmitis, its use should be limited to selected cases only.

POINTS TO PONDER

Another issue of relevance concerns the surgical technique that is used. Germs have a nasty habit of reproducing rather rapidly and our use of preop antibiotics may even result in naturally selecting more resistant strains. Germs entering the eye in the postop period through wounds that are not perfectly water-tight may be particularly virulent. Thus, any technique that may result in postop hypotony can potentially carry a higher risk of endophthalmitis. Once again, it is beyond the scope of this article to discuss the pros and cons of any single given procedure. Nevertheless, I believe "sutureless" surgery should be applied with some caution. Both anterior-segment surgeons using sutureless clear cornea cataract surgery as well as posterior-segment surgeons switching to small-gauge sutureless vitrectomy should not only consider the peculiarities of each specific patient but their own ability in constructing wounds that will not leak and lead to postop hypotony.

Personally, I am not embarrassed in placing a single stitch in all my clear-cornea cataract incisions, regardless of how good I may think my corneal tunnel is. Postop astigmatism is generally irrelevant and, if need be, the suture can be removed after 4 or 5 days. I must also confess that I still do a lot of soul searching when I opt for a sutureless small-gauge vitrectomy. How well sclerotomies will close with no suture probably has to do with many more variables than just wound construction itself, although this remains of paramount importance. Among these variables are the caliber of the system used (23-g vs. 25-g), thickness of the scleral wall, elasticity of collagen fibrils, and the amount of vitreous left behind.

Yet another point to ponder is represented by the often unspoken infective risks associated with the exponential rise that we will witness in intravitreal injections.

THE ENDOPHTHALMITIS VITRECTOMY STUDY

When we talk of postop endophthalmitis, we generally refer to the adverse event that ensues after cataract surgery. This is normal because the number of cataract procedures vastly outnumber the rest of ophthalmic surgeries. However, this does pose an important limitation because all the significant studies on postop endophthalmitis pertain to cataract surgery. As we shall discuss below, there is a great difference in the treatment of an infection that arises in the anterior chamber vs. an infection that originates within the vitreous itself.

For now, let us deal with endophthalmitis resulting from cataract surgery. The Endophthalmitis Vitrectomy Study (EVS) was published more than 10 years ago.¹ It has provided us with a wealth of information on a variety of issues pertaining to endophthalmitis and is appropriately considered a milestone on this specific topic.

However, the therapeutic indications that emerged from this extensive investigation are no longer applicable today. The EVS concluded that, as far as visual acuity (VA) was concerned, there was no significant benefit in the use of vitrectomy unless pretreatment VA had deteriorated to light perception. The study called for a vitrectomy to remove at least 50% of the vitreous with no attempt at inducing a posterior vitreous separation nor excision of cortical vitreous. In practice, what this meant is that the vitreous removed would be anterior without any attempt at removing the posterior vitreous, in direct contact with the macula. In short, not only the bacteria but their toxic products, as well as the body's own inflammatory response agents, would simply bathe the posterior pole for a prolonged time, even after vitrectomy had been carried out.

Thus, the main bias with this sort of approach is that vitrectomy is tardy and incomplete. Furthermore, VA is hardly an indicator of the severity of the infection.

So, was the EVS wrong? No, it was correct for its time. In 1995, equipment was not as efficient and safe as it is today and vitrectomy was sometimes looked upon as a "last resort" option by most physicians. However, today this is hardly the case. We have a number of technical advantages. Better machines and better probes allow greater flow control and the ability to work closer to the retinal surface. The use of temporary keratoprosthesis devices, as well as endoscopic vitrectomy, allows us to successfully bypass opacified corneas (corneal abscesses). Wide-angle viewing systems coupled with powerful light sources furnish a better view of the operating field. This is particularly important in giving the surgeon visual feedback of how his or her maneuvers on part of the retina (i.e., the posterior pole) are affecting the rest (i.e., the periphery). This accounts for a lower incidence of retinal detachment, which, it must be noted, the EVS had already found to be 260% higher in the nonsurgical group as compared to the vitrectomized one.

MANAGEMENT PHILOSOPHY

Our management philosophy aims at reducing the amount of bacteria and inflammatory material present within the eye and to do this before VA is irreparably damaged. Therefore, the "time factor" plays a crucial role. Endophthalmitis is thus better interpreted as a dynamic rather than a static process and, as such, it is better classified as either "early" or "advanced" rather than "moderate" or "severe."

As we have mentioned before, because VA can be misleading, when it comes to decision making it is best to rely on clinical appearance and course. What decisions are to be made when facing endophthalmitis?

If we are dealing with an infection that ensues within the vitreous as a result of an intravitreal injection or an infection resulting from a vitrectomy, there is no time to be lost. Because there is little or no vitreous buffer between the infection focus and the retina, a primary vitrectomy or a review vitrectomy must be carried out immediately. In dealing with infection arising from an intravitreal injection, complete vitrectomy is carried out. Removal of the lens or intraocular lens is generally not necessary. Once a certain amount of vitreous/liquid has been obtained for lab investigation, antibiotics will be used in the infusion liquid.

In cases where a vitrectomy has already been performed, complete removal of residual vitreous is necessary. Because there may be little residual vitreous, the infusion liquid containing antibiotics and entering the eye will dilute unpredictably with the liquid (balanced salt solution/aqueous) already present in the vitreous cavity. In such cases, I therefore like to carry out a fluid/air/fluid exchange so that I end up having a known concentration of antibiotics within the eye.

If, however, we are dealing with an infection arising in the anterior chamber, such as would be the case as a result of cataract surgery, a bit more time will be available before the infection reaches the retina. However, given the low incidence of complications associated with properly performed vitrectomy, I personally like to treat all these cases with complete and early vitrectomy (CEVE). I feel that postponing intervention may expose the patient to unnecessary risks. Furthermore, because of the need for close monitoring of the clinical evolution and presumably longer hospitalization period, more human resources may be required and higher costs sustained.

Nevertheless, other options are possible in cases that are detected early. The main features of these cases are generally represented by fibrin in the anterior chamber and a limited hypopyon. Fundus view is either hazy but still possible or a good red reflex is present. In such cases, it may be warranted to allow a few hours to go by before actually taking the patient to the operating room. During this time an aggressive regimen of topical antibiotic and steroid drops, as well as cycloplegics, should be commenced. Intravenous fourth-generation fluoroquinolones are administered. The patient is instructed to sit upright in bed so as to prevent pus from depositing on the macula. The clinical evolution is monitored very closely. If no improvement is detected within the following 24 hours, surgery should be no longer postponed.

I do not share EVS's enthusiasm for tap vitrectomy, which seems to carry with it only the risks of vitrectomy with few of its advantages.

SURGICAL STRATEGY

As with any vitrectomy, the purpose of the procedure is to reach the retinal plane. Unlike most vitrectomies, a number of obstacles hide the retina from the surgeon's view.

The corneal epithelium is scraped off if it is edematous. An anterior chamber maintainer is placed as fibrin and pus are removed from the anterior chamber and set aside for the lab.

There is generally no need to remove the intraocular lens, but a large posterior capsulectomy must be obtained so as to allow better perfusion of the capsular bag. Since some degree of choroidal congestion may be present, it is best to use a long (6 mm) infusion cannula. Once a sufficient amount of vitreous has been obtained for microbiology, antibiotics may be added to the infusion. If visibility is very poor, it is best to perform vitrectomy in a perpendicular, anteroposterior direction, nasally to the optic disc, rather than using sweeping movements on a horizontal plane. In such fashion, should the retina be detached and perforated, the amount of damage it would suffer would be less severe.

Once the posterior pole has been reached, a reasonable effort should be made to obtain a complete posterior vitreous detachment. The inflammatory process itself generally seems to facilitate this maneuver. Once posterior vitreous detachment has been achieved, gentle aspiration of debris with a silicone tipped extrusion needle should be carried out over the macular area. Depending on how good the view of the fundus is and on the condition of the retina, you should be more or less aggressive with the periphery. Ideally, it is good to know you have reached the ciliary body and have carried out a thorough vitrectomy with careful indentation. However, what really matters is the posterior pole (especially the macula), and it is better to leave some peripheral vitreous behind rather than to risk a retinal tear. Silicone oil tamponade is used only in those cases where such tears have occurred or where large areas of retinal necrosis have been identified. Patients are, once again, instructed to sit upright in bed at least for the first few days.

CONCLUSIONS

Endophthalmitis fulfills the criteria of a true abscess. It is a well-known fact in medicine that abscesses, wherever localized, must be drained. Presumably, the sooner this is done, the less amount of damage the retina will suffer. This concept seems to have been validated. In a recent report we published,² 91% of our patients had a best-corrected VA greater than or equal to 20/40, as opposed to EVS' 53%. Although the small numbers in our series cannot be directly compared with those reported in the EVS, they do have statistical significance.

These data, together with the rationale we have discussed, seem to justify an approach to endophthalmitis, which we have termed CEVE (Complete and Early Vitrectomy for Endophthalmitis). RP

REFERENCES

1. Vitrectomy Study Group. A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Arch Ophthalmol. 1995;113:1479-1496.

2. Kuhn F, Gini G. Ten years after… are findings of the Endophthalmitis Vitrectomy Study still relevant today? Graefes Arch Clin Exp Ophthalmol. 2005;243:1197-1199.