Therapeutic approaches for endophthalmitis

2016 Global Trends in Retina Survey Examines Treatment Options for Endophthalmitis

Summer 2017

How would you manage a patient with endophthalmitis following an intravitreal injection who has hand motion (HM) vision? What if that same patient had developed endophthalmitis following vitrectomy surgery?

SURVEY HIGHLIGHTS

Panelists

Africa/Middle East
Ahmed Y. El Khasha, FRCS, MD, ICO, EVRTS
Eye Consultants Center
Dubai, United Arab Emirates

Asia/Pacific
Yusuke Oshima, M.D., Ph.D.
Oshima Eye Clinic
Osaka, Japan

Central and South America
Mauricio Maia, M.D., Ph.D.
Federal University of São Paulo
Sao Paulo, Brazil

Europe
Stratos V. Gotzaridis, MBBS, MD
My Retina – Eye of Athens
Athens, Greece

United States
Mina Chung, M.D.
Flaum Eye Institute – University of Rochester
Rochester, New York

Here are some key findings. Survey responses are grouped into 5 regions for ease of analysis. We thank our thought leaders for participating in the following roundtable discussion of the 2016 survey.In the 2016 Global Trends in Retina Survey, 1,127 retina specialists from 39 retina societies answered these questions and more; we compared their responses to those of 689 U.S. ASRS members who answered the same questions as part of the 2016 Preferences and Trends (PAT) Survey.

How would you manage a patient with endophthalmitis following an intravitreal injection who has hand motion (HM) vision?

Ahmed Y. El Khashab – Africa/Middle East: The reported incidence of endophthalmitis following intravitreal injection varies significantly from 0.01% to 0.8% per injection, with the overall incidence reaching 0.05%, according to recent large-scale review articles.

For a long time, the Endophthalmitis Vitrectomy Study (EVS) remained the primary reference for the management of endophthalmitis, but over the past decade, numerous articles in peer-reviewed journals by Kuhn, Gini, and others have shifted the consensus toward earlier vitrectomy.

This explains why pars plana vitrectomy is the preferred procedure in the operating room by 70% in our region, as well as in Asia/Pacific, Central and South America, and Europe.

Yusuke Oshima – Asia/Pacific: Although we understand the EVS results and the recommended guidelines for treating infectious endophthalmitis following cataract surgery, the “tap and inject” approach should be the first-line treatment for patients with visual acuity equal to or better than HM.

We still believe that the most effective treatment options for preventing retinal necrosis and preserving useful vision are early vitrectomy to remove infected vitreous and intravitreal irrigation with antibiotics to flush out the bacteria or other microorganisms and their toxins from the vitreous cavity. In such an emergency situation, the most commonly used antibiotic for vitreous irrigation or for the “tap and inject” technique following vitrectomy is vancomycin.

Mauricio Maia – Central and South America: Endophthalmitis following intravitreal injection is a significant and not-so-rare complication that can lead to legal issues. For this reason, I believe colleagues around the world (with the exception of U.S. surgeons) feel more comfortable managing this significant complication in the operating room.

Perhaps U.S. colleagues are accustomed to performing injections in the office and/or base their treatment recommendations on EVS data; however, the EVS did not evaluate postinjection endophthalmitis. Local regulatory requirements and the medical malpractice environment—not just the medical literature—influence treatment decisions. Additionally, Latin American surgeons do not follow the EVS data regarding post-injection endophthalmitis due to advances in pars plana vitrectomy (PPV).

Stratos V. Gotzaridis – Europe: Small-gauge vitrectomy has become an easy-to-use surgical technique with fewer complications than ever before, and it is increasingly being performed on an outpatient basis. Trocars provide protection against entry-site tears. Powerful light sources allow for improved visualization, even in relatively dense, opaque environments.

If visualization is not adequate, performing even a simple core vitrectomy in an endophthalmic eye allows for the destruction of the lacunae (which contain the bacteria) and facilitates the penetration of antibiotics and steroids. In addition, flushing the vitreous cavity with the medications in the infusion line during vitrectomy provides immediate drug action. These factors may explain why PPV ranks far ahead of office-based tap-and-inject procedures in the survey as the preferred treatment in almost all regions.

Mina Chung – United States: We have no clear prospective evidence comparing vitrectomy to the ’tap and inject” approach in the management of post-injection endophthalmitis. A retrospective U.S. study reported better visual outcomes with the “tap and inject” approach, but of course more severe cases might be more likely to undergo vitrectomy, which is a limitation of a retrospective study. The preference of U.S. retina specialists for the “tap and inject” approach may also be influenced by geographic or systemic factors, such as longer travel distances to the operating room or other barriers to operating room access.

How would you manage a patient with endophthalmitis following vitrectomy surgery who has HM vision?

Ahmed Y. El Khashab – Africa/Middle East: Since the prognosis for post-PPV endophthalmitis is consistently poor, surgeons in Africa and the Middle East, like their European colleagues, appear to be divided on the initial management approach, with a greater tendency toward the more conservative “tap and inject” procedure performed in the office.

Not only is the "tap and inject" approach faster, but tapping a vitrectomized eye can easily provide a good specimen for identifying the causative organism and allows for more space for intravenous antibiotic injection with less risk of increased intraocular pressure.

Yusuke Oshima – Asia/Pacific: We believe that early revision surgery to extensively remove the residual vitreous skirt, combined with intravitreal irrigation using antibiotics to flush out the bacteria or other microorganisms and their toxins from the vitreous cavity, is the most effective treatment for preventing retinal necrosis, removing the scaffold for proliferation, and preserving useful vision. Vancomycin is the most commonly used antibiotic for vitreous irrigation or for the “tap and inject” technique following revision surgery.

Mauricio Maia – Central and South America: Endophthalmitis following PPV is a rare complication that may lead to legal issues. For this reason, I believe South American vitreoretinal surgeons feel more comfortable managing this important complication in the operating room.

In addition, early intervention in the operating room allows the surgeon to assess the condition of the retina, use silicone oil if necessary, and administer intravitreal medications. The difference compared to the United States, where the trend is moving in the opposite direction, may be related to the fact that American vitreoretinal specialists are comfortable performing intravitreal injections in their offices, according to the medical literature.

Stratos V. Gotzaridis – Europe: An eye that has already undergone vitrectomy provides better, more direct access to the bacteria during an office-based tap-and-inject procedure. This is why most regions (including Europe) have increased the use of this treatment. In most cases, once endophthalmitis is diagnosed, we perform a tap-and-inject procedure during the initial visit and schedule the patient for PPV the following day.

The prompt application of the “tap and inject” technique will provide immediate drug action. I prefer to enhance the drug’s effectiveness by reducing the bacteria’s living space. A fluid-gas exchange (1.5 ml of SF6) performed in the office (using a slit lamp) will reduce the living space by more than half, thereby enhancing the effectiveness of the medications within 24 hours.

Mina Chung – United States: Since post-vitrectomy endophthalmitis is rare, we may never be able to gather enough prospective data to answer this management question. At least from a theoretical standpoint, intravitreal antibiotic injection may penetrate more effectively in a vitrectomized eye, so the greater worldwide preference for the “tap and inject” approach in this scenario compared to the previous question seems logical.

Actually, I find it more surprising that the percentage of people in the United States who choose the “tap and inject” method has remained the same for post-injection endophthalmitis. Perhaps it’s because the proportion of respondents using the “tap and inject” method was already high.

How would you initially treat a 72-year-old patient with branch retinal vein occlusion (BRVO), macular edema, and visual acuity (VA) of 20/60?

Ahmed Y. El Khashab – Africa/Middle East: The survey shows an overwhelming consensus that anti-VEGF drugs are the first-line treatment for macular edema in BRVO worldwide.

Despite the fact that Avastin (bevacizumab, Genentech, Inc., South San Francisco, CA) is an off-label drug and is banned in some countries in the Gulf region, 3 out of 4 respondents from the Africa/Middle East region chose it as their primary treatment. This is primarily due to cost considerations and Avastin’s comparable efficacy, which has been demonstrated in studies such as the DRCR.net Protocol T for other indications, such as diabetic macular edema.

Compare this with the results of an ASRS Preferences and Trends (PAT) Survey trend question regarding the treatment of wet AMD, in which, between 2012 and 2016, an increasingly large majority of respondents worldwide said they would choose Eylea (aflibercept, Regeneron Pharmaceuticals, Inc., Tarrytown, NY) or Lucentis (ranibizumab, Genentech, Inc.) over Avastin if all three medications cost the same.[5]

Yusuke Oshima – Asia/Pacific: The Japanese Ministry of Health, Labor, and Welfare does not officially approve the use of Avastin for ophthalmic diseases, including age-related macular degeneration (AMD), retinal vein occlusion (RVO), myopic choroidal neovascularization (CNV), or other ocular neovascular diseases.

So even though we know that Avastin is much cheaper than Lucentis, most retina specialists prefer Lucentis because its use is officially approved, and it is an evidence-based drug for treating RVO-associated macular edema. Another reason may be that we do not have compounding pharmacies in Japan that can regularly aliquot Avastin into small syringes for single-dose injections.

Mauricio Maia – Central and South America: I believe the higher rates of Lucentis use in South America may be related to:

1. Reimbursement by insurance companies (which generally do not cover Avastin)
2. Lobbying by the pharmaceutical industry
3. The possibility of problems when Avastin is aliquoted in pharmacies that may not adhere to high standards for such procedures, thereby increasing the risk of endophthalmitis

BRAVO is the pivotal study that evaluated the use of Lucentis for BRVO. However, the high rates of Avastin use in Africa, the Middle East, and the United States are based on evidence of Avastin’s efficacy for BRVO, its superior cost-effectiveness, and reimbursement policies.

Stratos V. Gotzaridis – Europe: The response from nearly all regions surveyed is in favor of Avastin, with the exception of Central and South America.

Avastin is a low-cost medication available to every medical practice. It offers the advantage of being readily available for immediate use as soon as a diagnosis of BRVO-related macular edema is confirmed. Once the first Avastin injection has been administered, the practitioner and the patient have time to schedule the next anti-VEGF treatment, which may be Avastin again, Lucentis, or Eylea. Countries where Avastin is not available for ophthalmic use will, of course, treat patients with either Lucentis or Eylea from the outset.

The paradox revealed by this survey is that Avastin is used by more than 70% of respondents in two regions with vastly different economic conditions: Africa/Middle East and the United States. The low cost of the medication, combined with its efficacy, must be the reasons for its widespread use.

Mina Chung – United States: It is interesting to note that U.S. retina specialists prefer Avastin for treating macular edema in BRVO—a preference comparable to its use in Africa and the Middle East—and this is presumably due to its cost-effectiveness. Avastin would be my first-line choice in this setting, for cost reasons.

The regional variability in preferences for the different anti-VEGF agents highlights the lack of a multicenter clinical trial comparing Avastin and Lucentis, or Eylea, for BRVO.

References:

1. Schwartz SG, Flynn HW, Scott IU. Endophthalmitis following intravitreal injections. Expert Opin Pharmacother. 2009;10(13):2119-2126. doi:10.1517/14656560903081752.
2. Moshfeghi AA, Rosenfeld PJ, Flynn HW Jr, et al. Endophthalmitis following intravitreal vascular endothelial growth factor antagonists: a six-year experience at a university referral center. Retina. 2011;31(4):662-668. doi:10.1097/IAE.0b013e31821067c4.
3. Kuhn F, Gini G. Ten years later … are the findings of the Endophthalmitis Vitrectomy Study still relevant today? [published online September 2, 2005]. Graefes Arch Clin Exp Ophthalmol. 2005;243(12):1197-1199.
4. Chaudhary KM, Romero JM, Juan M, Ezon I, Fastenberg DM, Deramo VA. Pars plana vitrectomy in the management of patients diagnosed with endophthalmitis following intravitreal anti-vascular endothelial growth factor injections. Retina. 2013;33(7):1407-1416. doi:10.1097/IAE.0b013e3182807659.
5. Stone TW, ed. ASRS 2016 Preferences and Trends Membership Survey: Chicago, IL. American Society of Retina Specialists; 2016.

Financial Disclosures

Dr. Chung – LOWY MEDICAL RESEARCH INSTITUTE: Consultant, Grants; SANTEN INC: Consultant, Honoraria; WAVE LIFE SCIENCES: Consultant, Honoraria.

Dr. El Khashab – ALLERGAN INC: Consultant, honoraria; BAYER HEALTHCARE: Consultant, honoraria; NOVARTIS PHARMACEUTICALS CORPORATION: Consultant, honoraria.

Dr. Gotzaridis – ALCON LABORATORIES, INC: Advisory Board, Honoraria.

Dr. Maia – ALCON LABORATORIES, INC: Consultant, Speaker, Honoraria; ALLERGAN, INC: Consultant, Investigator, Speaker, Grants, Honoraria; BAUSCH+LOMB: Consultant, Speaker, No Compensation Received; BAYER HEALTHCARE PHARMACEUTICALS, INC: Consultant, Speaker, Honoraria; BRAZILIAN NATIONAL COUNCIL FOR RESEARCH (CNPQ): Consultant, Investigator, Grants, Honoraria; COORDINATION FOR THE IMPROVEMENT OF HIGHER EDUCATION PERSONNEL (CAPES): Consultant, No Compensation Received; SÃO PAULO STATE RESEARCH FOUNDATION (FAPESP): Consultant, Investigator, Grants, Honoraria; KEMIN PHARMA: Advisory Board, Consultant, Investigator, Speaker, Grants, Honoraria, Intellectual Property Rights; NOVARTIS PHARMACEUTICALS CORPORATION: Advisory Board, Consultant, Investigator, Speaker, Grants.

Dr. Oshima – ALCON LABORATORIES, INC: Speaker, Equipment (Department or Practice), Honoraria; DUTCH OPHTHALMIC RESEARCH CENTER (DORC): Speaker, Equipment (Department or Practice), Honoraria; NIDEK INC: SPEAKER, EQUIPMENT (DEPARTMENT OR PRACTICE), HONORARIA.

Dr. Shah – ALLERGAN INC: Advisory Board, Consultant, Equipment (Department or Practice), Honoraria; BAUSCH+LOMB: Speaker, Honoraria; JOHNSON & JOHNSON: Speaker, Honoraria; QLT INC: Consultant, Speaker, Honoraria; REGENERON PHARMACEUTICALS, INC: Advisory Board, Consultant, Speaker, Honoraria.