VBS VI: Women of VBS Breakfast -- Going Beyond Boundaries


Hanna Hui, Yoshihiro Yonekawa Mass Eye & Ear / Harvard Medical School Glenn Jaffe, M.D. is the Robert Machemer Professor of Ophthalmology and Chief of the Retina Division at Duke Eye Center. He is a world-renowned vitreoretinal surgeon, uveitis expert, illustrious scientist and clinical trialist, reading center guru, generous educator, and an esteemed editorial board member of RETINA. Dr. Jaffe is famous for a diverse array of contributions to our field, but today, we hope to share with you his clinical pearls on how to approach patients with uveitis, with a focus on vitreoretinal surgery. We had the opportunity to speak with Dr. Jaffe this week. Please see below our transcribed conversation. We hope that you enjoy learning about how he methodically tackles these tough cases. Uveitis vitreoretinal surgery is a unique hybrid subspecialty that helps patients with some of the most difficult pathology. How did you end up merging the two disciplines?

Early Inspirations

[caption id="attachment_2165" align="alignleft" width="320"]Glenn Jaffee Glenn Jaffe, MD[/caption] Jaffe: I was a resident at UC San Francisco where there is a unit called the Proctor Foundation, which is oriented towards the treatment and research of uveitis and external inflammatory diseases. I became interested in uveitis because there were really great mentors there and people who were quite well known in uveitis at the time. Simultaneously, I also had great retina mentors, who inspired me to enter their field. One of whom was Alex Irvine, who was a retina specialist at UCSF and the other was Howard Schatz, who, at the time, was a very well-known retina specialist and is now a world famous photographer in New York.

The Need for a Uveitis Specialist

I trained at Medical College of Wisconsin as a vitreoretinal surgery fellow, but still retained the interest in uveitis. When I came to Duke, there was really a need for somebody to do uveitis - there was no specialist. And so I thought it would be a great combination to have a general vitreoretinal practice, but then also a subspecialty uveitis practice.

Uveitis from a VR Surgeon's View

I look at uveitis patients from a posterior segment surgeon’s perspective, so some of my management strategies might be a little different from an ophthalmologist who is either a medical uveitis specialist, or a uveitis specialist who doesn’t do posterior segment surgery. Having a comfort level of knowing the indications for vitreoretinal surgery and being able to perform the surgeries for the patients myself can be a nice advantage. What kind of uveitis surgeries did you perform most commonly when you started your career? And how has that changed over time to the current indications? This has evolved over time. Overall, I would say one of the most common procedures would be vitreous biopsies: when you start a patient on an empirical therapy and they don't respond the way you expected them to, or when you suspect cancer or infection. Diagnostic vitrectomies can be performed as a part of therapeutic vitrectomies as well. Let’s say the patient has dense vitritis, and I am worried about lymphoma or endogenous endophthalmitis. The biopsy establishes the diagnosis, but the vitrectomy also clears the vitreous cavity to improve vision. Other situations might be epiretinal membrane in the setting of a diagnosis still in question. For example, I had a patient who we were suspecting to have toxocariasis but he was older than your average patient with toxocariasis. He had an epiretinal membrane distorting the fovea with a white lesion on the optic nerve, so I did a vitrectomy to peel the membrane and the lesion, and sent the sample for histopathology. The lesion was an eosinophilic granuloma, and the vitreous sample was positive for toxocara. At the same time, his vision improved because of the removal of the epiretinal membrane. [caption id="attachment_2162" align="alignnone" width="1140"]ASRS-RIB-Image-1283 Epiretinal membrane in uveitis from the ASRS image bank. Unrelated to case described in text.[/caption] There was a period when we used to place a lot of ganciclovir implants for CMV retinitis associated with AIDS. The implant isn't even available anymore because of the fortunate decline in AIDS and CMV retinitis. After that I started doing more fluocinolone acetonide sustained drug delivery implants, the Retisert, for patients who needed long term control and who either were not responding or were not tolerating systemic immunosuppression, but who did respond to steroids, or if they had very asymmetric disease and the patient didn’t want to go on any immunosuppresives. So for quite a few years that was a relatively common procedure that I performed, either in combination with therapeutic vitrectomy for another indication, or in combination with glaucoma tube surgery or cataract extraction. So I often did these cases as combination procedures with my glaucoma and anterior segment colleagues. Over the last few years, I have not placed as many Retiserts as I had previously. Instead, I have performed more injectable fluocinolone acetonide intravitreal sustained drug delivery implant procedures, performed in the outpatient clinic, initially as part of an individual investigator protocol, and more recently as part of a Phase III study. Currently we are awaiting approval by the FDA of these implants, which will hopefully happen within the next year. Some of this is dating me, but we also used to do submacular surgery in the early years when I was starting out. This was before anti-VEGF therapy was available, so we would do, as an example, submacular membrane removal in patients with presumed ocular histoplasmosis. The indications for vitreoretinal procedures have been evolving, and the indications have been expanded. Currently, it includes more standard vitreoretinal surgery indications, for example, tractional retinal detachment, rhegmatogenous retinal detachment, epiretinal membrane, etc. in addition to diagnostic vitreous biopsies and intravitreal sustained drug delivery implants. It's really been a revolution over the years since I’ve been here. [caption id="attachment_2164" align="alignnone" width="990"]Glenn Jaffe Glenn Jaffe, MD[/caption] Can you tell us about your strategies and philosophies regarding perioperative inflammation control? I would like to have the eye as quiet as possible before the surgery. To me, the most important thing to get quiet is the anterior chamber or the iridocyclitis, because when you operate on patients who have active anterior segment inflammation, bad things can happen. For example, severe hypotony can occur with fibrinous reactions and posterior synechiae that are difficult to control. So to the extent possible, I like to obtain a quiet anterior segment. Beyond that, I’m not as concerned about vitritis and posterior segment inflammation. Usually the surgery you are doing is trying to address the posterior segment inflammation. When placing Retiserts, I would also minimize the number of scleral incision to avoid hypotony. When a second Retisert is necessary in the eye, I prefer to go in the old incision to remove the old implant out of the original scleral incision, and place the new one into the same scleral incision, assuming that the conjunctiva and the sclera are healthy. Also, if I’m doing an exchange, I always place an infusion line since I don’t want the globe to collapse because it’s otherwise procedure very difficult to control any bleeding, unless you’re doing a full vitrectomy as part of this. [caption id="attachment_2161" align="alignnone" width="3024"]ASRS-RIB-Image-719 Retisert image from the ASRS Image Bank.[/caption] Stephen Foster championed the teaching of having a quiet eye for three months prior to doing cataract surgery in eyes with uveitis. This is sound advice for patients who are not undergoing simultaneously a procedure to place a long-acting corticosteroid delivery system. In contrast, for patients who are getting a steroid implant, as long as I can get the anterior segment quiet, I don’t wait any length of time. I just do it once the anterior segment is quiet and then combined surgeries seem to work well. What are your pearls for preoperative assessment? Preoperative evaluation and ancillary testing prior to the surgery are very important. Often, these patients have media opacities, such as cataract, vitreous hemorrhage and vitreous opacities. In this situation, where it isn’t possible to clearly see the posterior segment we’ve shown that you can identify macular edema pretty accurately on an ultrasound. You certainly want to know if you’re going to be repairing a retinal detachment or if you’re just removing vitreous opacities, and knowing that there’s macular edema may prompt you to give a perioperative periocular or intravitreal steroid injection. [caption id="attachment_2163" align="alignnone" width="1504"]ASRS-RIB-Image-13233 Retinal detachment in uveitis, from the ASRS Image Bank.[/caption] Do you always pulse your patients with solumedrol? I definitely do not always pulse. It really depends on what has been required during the treatment course leading up to the surgery to keep the eye quiet. So if it’s combined cataract surgery with vitreoretinal surgery, we might put them on prednisone for a week or so before the procedure then keep them on it for a week to two weeks after. The length of time is dictated by the degree of inflammation. If they have been requiring systemic corticosteroids leading up to the procedure just to get the eye quiet and I’m not doing it prophylactically but actively having to treat the inflammation, then I would be more likely to pulse them with solumedrol at the time of the procedure. What is your technique for vitreous biopsy?

Are There Cells?

For vitreous biopsy, the first thing I want to know is if there’s a chance that I’m actually going to get something from the biopsy. It can be very helpful to do transillumination of the pupil so you can see the cells in the vitreous, and you should also be able to see them—just as you can from the slit lamp exam. If you cannot see cells, the chance of getting a positive biopsy is low, if you’re obtaining cytopathology to try to establish a diagnosis.

3-Port vs 1-Port

I like a 3-port approach to the vitreous biopsy. Some do single port but I’d like to get as much of the sample as I can, which is possible with 3-port vitrectomy. I also like to see what I’m doing to avoid hitting the lens and retina, so having good illumination and wide angle viewing with 3-port really helps.

Diluted vs Undiluted

The first decision is: do I need an undiluted sample or is a diluted sample okay? At least at Duke, the cytopathology laboratory feels that they get better samples from diluted samples, from which they do a cytospin to prepare the cells for analysis. The flow cytometry laboratory wants the maximum number of cells possible, whether I obtain a diluted or undiluted sample. But if we’re doing vitreous antibody testing, then I want an undiluted sample. If we’re testing for an infection that’s getting cultured, we can certainly use the diluted sample, but you may be a little more likely to get a positive result if you use an undiluted sample.

Intraoperative Pearls

Typically to obtain the undiluted sample, we collect the samples first with the infusion off, and at least for the Constellation, you have to trick the machine into thinking the infusion is actually running, so you turn the infusion down to zero or otherwise the cutter won’t work. The surgeon is looking in the scope, and is cutting, and the cutter is attached to an extension tube that’s connected to a syringe, typically a 10 mL syringe. The assistant is looking in the microscope and glancing back and forth at the syringe and the microscope and whatever volume of air from the tubing dead space that is aspirated into the syringe is going to be the volume of fluid that’s removed. Typically, that fluid ends up in the dead space of the tubing. Then I disconnect the syringe and gently blow the fluid back out the end of the vitrector into a microcentrifuge tube. If it’s undiluted vitreous, or if just aspirated into the 10mL syringe and keep it in the 10mL syringe if it’s for the diluted sample.

Communicating with the Lab

I would say the most important aspect of this communication is to know what you’re going to do before you collect the sample and which lab you’re going to send it to. There’s always the question as to how you handle the sample and whether you put it in particular media. We’re very fortunate now that our cytopathology lab is right downstairs from the operating room and we can carry it down there and they’ll process it immediately when they see us, so there’s really no lag time. But if it is a diluted sample, and if there is going to be a lag time, it makes sense to put the sample in RPMI to preserve the cells.

How do you perform your choroidal biopsies?

There are two ways to do a choroidal biopsy. You can do it externally, or you can do it internally. If the lesion is anterior, you may take an external approach where you create a scleral flap, and then diathermize the borders and then incise the lesion ab externo. That’s something I don’t really do very often. An ocular oncologist might be more likely to take this approach. For an internal biopsy, it depends on the sample you’re actually trying to obtain. If you’re trying to remove a lesion in toto, then we might diathermize the borders around it, raise the bottle pressure or the infusion pressure, and then cut around the lesion with scissors. You might consider doing the biopsy by taking the sample from the junction of the normal and the abnormal tissue. You can also do a transvitreal biopsy with the vitreous cutter. For example, you can go directly into the lesion with the 25-gauge cutter. You again want to raise the bottle or the infusion pressure, and then with the cutter connected to extension tubing, the assistant can aspirate during the cutting. You are essentially getting chunks of tissue into the vitreous cutter that you can then send to pathology. Typically, the indications for doing the choroidal biopsy or chorioretinal biopsy are if you’re suspicious of cancer or if you if you have an undiagnosed infection. But this is after other testing has been accomplished and I haven’t come up with other less invasive methods. For example, I would certainly do PCR testing in the clinic if we are suspecting herpetic infections or CMV, and then I might do a vitreous biopsy if the results are inconclusive, and if that still doesn’t give an answer and the patient is still progressing, then I might do the chorioretinal biopsy. What are the top Glenn Jaffe pearls for approaching surgery in uveitis patients? Having done this for a long time, I would say that the vitreoretinal surgeries for patients with uveitis are some of the most interesting surgeries we do. It combines the typical vitreoretinal surgical techniques often with establishing a diagnosis, and we can offer more for our patients. I would say that the most important thing is to get the anterior segment quiet to the extent possible before vitreoretinal surgery. Also, if you’re doing a diagnostic vitrectomy, make sure that you talk to the various people in different labs so that they know the sample is coming, so the sample isn't sitting somewhere overnight where the cells get ruined. Thank you so much Dr. Jaffe for sharing your many pearls on how to approach uveitis from the vitreoretinal surgical perspective.