Treat post-op endophthalmitis early to keep sight

By Ana Hidalgo-Simón MD

SUSSEX, UK - Comprehensive diagnostics and prompt aggressive therapy are essential elements for sight-saving therapy for postoperative endophthalmitis, according to the stringent protocol adopted at London's Moorfield Hospital.

Susan Lightman MD stresses that junior doctors and nurses there are generally the first to see these patients and need to be able to recognise the signs and to act swiftly.
Moorfield's counsels community ophthalmologists to treat postoperative endophthalmitis early with a standardised protocol. They suggest that patients only be transferred to Moorfield's if they are not improving.

"In the majority of cases the cause of lens extraction could be traced to chronic inflammatory problems rather than infections, but endophthalmitis can occur in eyes implanted with all types of lens," she explained.

The preliminary differential diagnosis between infection and inflammation frequently has to be made on clinical signs and symptoms only. A major problem is the very low rate of microbial culture in patients with endophthalmitis.

"There are many reasons for this. Many patients have received topical postoperative antibiotics. The number of microorganisms needed to cause an infection could be relatively low, or the microorganisms may be sequestered.

Finally, the culture conditions need to be very specific to be successful. But when we use highly sensitive techniques such as PCA, we know that we can find microbes in 100% of patients with clinical endophthalmitis," Dr Lightman noted.

Watch for lid swelling and new pain
Clinical signs indicating the early stages of eye infection are pain, eyelid swelling and reduced vision. Eye-lid swelling is particularly telling; although present in around 14% of patients, according to a recent study, lid swelling is frequently not documented as a relevant sign in the initial exploration.

When present, it is almost always due to infection rather than inflammation.
"The pain described by these patients is also different. The patient can generally tell very precisely when this new pain started, and can differentiate it clearly from the postoperative pain which is generally less intense.

"Postoperatively reduced vision is also a key sign. Most surgery-related inflammation is in the anterior segment. Any uvitritis should start alarm bells ringing immediately," Dr Lightman stressed.

Another key observation is the rapidity of the changes within the eyes. When a patient returns to the clinic within 24 hours of the operation with pain and inflammation, it is generally worth observing them for a couple of hours.
Pain, inflammation and swelling can change dramatically during that period of time. Rapid changes are nearly always linked to infection, especially to changes in visual acuity or vitreous changes.

Act now and transfer later
Dr Lightman emphasised that swift and effective treatment when the patient's vision is still 6/6 leads to the best results. Since all interventions have risks and drug treatments have side effects, the clinician needs to balance carefully the risk/benefit ratio before intervening.

"We need to be as sure as we can that we are dealing with an infection. Our actions need to be justifiable. <Your clinical judgment needs to see the current situation as being more compatible with infection than with inflammation>," she said.
Delaying treatment almost inevitably leads to bad visual outcome. Few eyes will recover vision. If it is already too late, the treatment will aim to avoid globe extraction, not to recoup vision.

"We have performed a study recently in which it is clear that patients who present with low vision will remain at the lower end of the visual range six months down the line," she remarked.

The deterioration can be extremely quick. In a matter of hours a patient can move from 6/6 to 6/60. Early intervention can maintain a considerable amount of vision. Dr Lightman strongly recommended treating these patients locally.
<"Don't transfer these patients to a specialist centre because time is of essence.> Sometimes we admit patients who have been sent to us with a 6/12 vision from another centre. In these four or five hours they are at counting fingers with a much worse prognosis," she explained.

In most cases it is just not enough to put the patient on topical antibiotics. Rather, it is necessary to use aggressive intraocular antibiotics. It is important to take samples and cultivate the causative microorganisms. Samples are required from both the aqueous and the vitreous humours.

"Our results found that when you take a sample of aqueous, the positivity rate is only 14%. The positivity rate when culturing vitreous samples is much higher at 86%.
"To take a vitreous sample is more tricky, but the positivity justifies it. We found no examples in which both aqueous and vitreous samples tested positive. So take samples of both," she advised.

A standardised protocol
Dr Lightman shared the standardised procedure for early stages of treatment of endophthalmitis used in her department at Moorefield's.
"We looked at a protocol to implement immediately after diagnosis, assuming that the microbiology samples won't be ready until the morning," she said.

Patients receive topical chloramphenicol, intravitreal vancomycin, amikacin or ceftazidime and oral ciprofloxacin.

Studies of the sensitivity of microorganisms cultured from endophthalmitis patients to these antibiotics confirmed the value of this protocol. A study found that 100% of them were sensitive to at least one of the antibiotics: 33% of patients were sensitive to one antibiotic; 55% to two; and 12% were sensitive to all three antibiotics used.

"The sensitivity analysis confirmed that this is a useful regimen to start with. Some ophthalmologists prefer to use ofloxacin instead of chloramphenicol but I believe chloramphenicol is much better. Some people use kleptacytim because of the fear of renal toxicity with amikacin. In fact the UK academy guidelines don't recommend the use of amikacin," she said.

But Dr Lightman continued to use amikacin after looking at all published evidence because the toxicity is sporadic and its broad spectrum is not achieved by the available alternatives, particularly for Gram negative microorganisms. She added that the department has known many instances of eyes treated with amikacin which have recovered or maintained vision.

Steroids have a role
She acknowledged that the use of steroids in this type of patient is controversial but nonetheless believes that topical and systemic steroids are greatly beneficial. The considerable inflammation caused by the infection and the treatment can be dampened by systemic steroids.

<"We initiate steroidal treatment one day after the initiation of the antibiotic regimen.> We use that timing to make absolutely sure that there are no fungi in the eye. Topical steroids are also extremely useful, but you need to be aware that when you are pouring steroid on top of the antibiotics, the corneal epithelium is taking a battering," she advised.
Her department's approach is not to give these patients drops through the night. She notes that the patients are in a great deal of pain and drops every few hours through the night do not help.

When bacteria find their way into an IOL (or an endotracheal tube or a catheter), it surrounds itself with a tough protective layer of biofilm that antibiotics find difficult to penetrate. Clarithromycin can help break down biofilm, exposing the bacteria to the action of the antibiotics again.

"We studied the effect of clarithromycin on patients with endophthalmitis. The results showed it to be effective only in the culture negative group. It just wasn't effective in culture-positive patients," she said.

Dr Lightman argued that the reasons for these results may be due to lower inoculums of microorganisms or the fact that culture-negative patients frequently have peculiar bugs which are not very virulent. Her current approach is to start patients on clarithromycin until the results from the culture laboratory arrive. If they are positive, clarithromycin is discontinued.

Enter anti-thrombotic therapy
She noted that fibrin is a big problem in postoperative inflammation. It has been frequently observed that patients with fibrotic deposits in the eye respond poorly to antibiotic treatment; they don't tend to do very well until the fibrin is removed.
Tissue plasminogen activator or tPA is used to dissolve blood clots in conditions such as acute myocardial infarction and early stage stroke. It is not licensed for ocular use. Dr Lightman has given tPA (25g in 0.1ml into the anterior chamber) to patients with endophthalmitis, with promising results.

"You see the pupil dilating almost immediately and the fibrin shrinks. By the following morning you have a very different situation. The antibiotics and steroids can penetrate and the full eye starts to settle. We use it a lot, although it is very expensive. You can make the most of it by aliquoting it in insulin syringes and keeping it frozen in the pharmacy, using only the small amount required in each eye. It is very effective," she said.
With aggressive treatment, most of these patients will settle in 48 hours. Once the pain is receding and the medication is acting, the patient can be sent home for two or three days until the eye reverts to a more normal state.

If in 48 hours the situation looks worse or the same, Dr Lightman's recommendation is to repeat the intravitreous antibiotics, this time with an indication from the microbiology laboratory whether the culture is positive. If after that second round of therapy, and another 48 hours wait, the situation is not better, she suggested that vitrectomy might be considered.

"We have decided not to use the early vitrectomy approach in these patients. The complication rate is very high and it is very difficult to do well because the eye is in such condition," she said.

For chronic endophthalmitis her approach is to treat patients with vancomycin and oral antibiotics but not to give them steroids. Steroids may provide a temporary respite, but the infection will return as soon as they are stopped.
If aggressive antibiotics do not resolve the infection, the IOL may need to be removed because the microorganism is sequestered at the back and cannot be eliminated.
Dr Lightman spoke at a one day conference on foldable IOLs sponsored by Rayner.

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