Brian K. Do, MD
The Retina Group of Washington
The second session of 2018’s Retina Subspecialty Day, moderated by Maria H. Berrocal, MD, and John W. Kitchens, MD, introduced a number of innovative surgical technologies, techniques, and approaches within the realm of vitreoretinal surgery.
A New Way to Close Holes and Breaks
Stanislao Rizzo, MD, Chair of the Department of Ophthalmology at the University of Florence, in Italy, presented the first talk of this surgical session, in which he discussed a novel use of a familiar biomaterial in the closure of macular holes. He began his discussion by presenting a not-terribly-uncommon challenge in the practice of vitreoretinal surgery: failed macular hole surgery. Numerous techniques have been described over the past several years for these types of scenarios, including various types of internal limiting membrane (ILM) flaps and autologous retinal transplantation.
Dr. Rizzo described his use of human amniotic membrane as an adjunct in the closure of macular holes, which has not previously been described. Prior to attempting its use in human subjects, Dr. Rizzo and his colleagues proved its safety in rabbit eyes; it remained for substantial periods of time within the subretinal space in 10 rabbit eyes without any obvious signs of immunogenicity.
In 12 macular hole surgeries (in individuals who had previously failed conventional surgical intervention), 3 of which were performed in eyes with high myopia, human amniotic membrane was placed over the macular hole at the end of surgery, ultimately resulting in a 100% closure rate. Final best-corrected visual acuity in these cases ranged from 20/800 to 20/70, and no post-operative complications were noted.
Dr. Rizzo’s presentation suggests another potential weapon in our armamentarium in the fight against recalcitrant macular holes, and may even provide a way to close peripheral retinal breaks without endolaser.
Hypersonic Vitrectomy: Continued Clinical Experience and Technical Improvements
The second talk of the session was presented by Carl Awh, MD, of Tennessee Retina. Hypersonic vitrectomy, which involves the use of ultrasonic power in vitreous removal, is a technology on which Dr. Awh has presented previously, and this meeting’s discussion was meant to serve as an update on clinical outcomes thus far.
For those unfamiliar with the details of the technology involved, the hypersonic vitrectomy probe is capable of 1.7 million “cuts” per minute, creating a localized region of tissue disruption just within or at the surface of the vitrector port, leading to a phenomenon called “hypersonic liquefaction.” This liquefaction results in improved flow through the vitrector handpiece, especially when compared to that seen with traditional guillotine vitrector handpieces.
Dr. Awh proceeded to share the results of a Fall 2017 prospective trial conducted by himself and Dr. Kevin Blinder, MD, of the Retina Institute of St. Louis, in which both surgeons performed a consecutive case series of 84 vitrectomies. 64 of the 84 cases were performed using a 23G hypersonic vitrector, and the remaining 20 with a traditional guillotine cutter; all were completed successfully. When looking at machine parameters, there were no significant differences in irrigation fluid use, time of active aspiration, or actuation duration between the hypersonic and traditional vitrector. Of note is that the average vacuum required when using the hypersonic vitrector was lower than that used with the conventional cutter.
2 complications were noted in the cases performed with the hypersonic vitrector: 1 iatrogenic retinal break in an area of detached retina, as well as 1 case of IOL-pitting during capsulotomy.
In a brief video presentation, Dr. Awh further demonstrated the capability of the hypersonic vitrector to trim and strip epiretinal membranes, which appears to be much easier with the vitrector port occluded. Another potential benefit of this handpiece is the ease with which dense nuclear material can be removed from the vitreous cavity, without the use of a fragmatome.
Following the completion of these 84 consecutive cases, the study was paused, and modifications were made to the vitrector port and handpiece. Over 100 cases have been performed by 9 surgeons since September of 2018, with no noted complications. Pre-operative diagnoses in the cases for which the hypersonic vitrector was used include:
- Vitreous opacities
- Macular epiretinal membrane
- Macular hole
- Retained lens material
- Rhegmatogenous retinal detachment
- Proliferative diabetic retinopathy
- Vitreous hemorrhage
- Tractional retinal detachment
- Retained silicone oil
While the utility and versatility of the hypersonic vitrector handpiece has yet to be fully demonstrated, there certainly appear to be clinical situations in which this technology can be equally effective as that seen with traditional guillotine vitrectomy. The benefit of near-equal flow through the handpiece with a port size 1/3 of that seen with traditional cutters is worth noting a well.
Development of a Deep Learning System for Digitally Enhanced Internal Limiting Membrane Peeling
Shifting the focus of discussion to the use of an artificial intelligence (AI) – based system as a surgical adjunct, Kazuaki Kadonosono, MD, of the Yokohama City University School of Medicine’s Department of Ophthalmology and Micro-Technology, proposed the investigation of a deep learning approach to accurately identifying the ILM during surgery, while minimizing the use of dyes. He suggested that a deep learning system for digitally enhancing membrane peeling could prove to be an invaluable surgical tool in the treatment of macular holes and/or other retinal diseases such as epiretinal membrane (ERM), diabetic macular edema (DME), and proliferative vitreoretinopathy (PVR).
He noted that in conventional macular surgery in which the ILM is peeled, dyes are routinely used to stain the ILM intra-operatively; he also suggested that even stained ILM could be difficult to observe in highly myopic eyes, eyes with DME, and those with PVR. Additionally, he raised the issue of potential toxicity to the retinal pigment epithelium (RPE) and retinal photoreceptors when using ILM-staining dyes like indocyanine green or brilliant blue.
With the digital enhancement of images obtained using 3D visualization systems, Dr. Kadonosono suggests that one can observe ILM more clearly. Changing digital parameters within the visualization system (like HUE) has proven useful, allowing differentiation of the ILM from underlying layers. Software that uses a special algorithm to aid enhancement has also been developed; limitations still exist when treating eyes with myopia or pathologic ILM.
In a proof-of-concept study, Dr. Kadonosono used an automated AI method to analyze images of the macular region in 19 eyes with macular hole, and 12 with ERM, in which the ILM had been stained intra-operatively with dye, and concluded that these algorithms and technological adjuncts could be helpful in minimizing the use of dyes in ILM peeling through improved ILM visualization.
Final Visual Acuity, Not Amount of Improvement, Must Be the Measure of Our Success in Epiretinal Membrane Surgery
Colin A. McCannel, MD, of the University of California – Los Angeles, began this philosophical discussion on ERM surgery with some staggering numbers: patients in Los Angeles pay as much as $10,000 per eye out of pocket on top of insurance / Medicare reimbursement, an indicator of the price individuals place on good vision. He used this to assert that we, as vitreoretinal surgeons, should also strive for excellent visual acuity outcomes when performing surgery for ERM / macular pucker.
Dr. McCannel spoke about the need for vitreoretinal surgeons to modify our approach to determining what qualifies as a successful visual outcome following epiretinal membrane surgery. In particular, he argues that vitreoretinal surgeons should aim for a final visual acuity of 20/20-20/25 and minimal metamorphopsia in patients who have undergone epiretinal membrane peel. He also raised questions of potential benefit in earlier intervention, which must be weighed against potential surgical risks. He cited a low risk of major complications of vitrectomy – retinal detachment (cited as 1-2% risk) and endophthalmitis (cited as approximately 1/2000 – which is lower than the approximately 1/1000 cited for cataract surgery); these rates may be declining.
One of the issues presented by Dr. McCannel with previous studies on surgical outcomes is that the majority of studies tend to report visual acuity improvement, as opposed to final visual acuity; this does not allow us to properly predict the likelihood of achieving excellent visual acuity. His stance is that we need better guidance from clinical research.
Dr. McCannel presented the results of a pilot study he conducted, the results of which indicate overall that final visual acuity is heavily dependent on pre-operative visual acuity. In individuals included in this study, a pre-operative best-corrected visual acuity (BCVA) of 20/30 or better was 100% correlated with final BCVA of 20/25 or better; this likelihood dropped to 48% when pre-operative BCVA was 20/40 to 20/60, and to 30% when 20/70 or worse. In regard to complications, there were zero cases of post-operative endophthalmitis, and 1 retinal detachment (2%). All of the eyes but one included in the pilot study had improved BCVA post-operatively; all were pseudophakic at the end of the study.
While additional studies likely need to be completed prior to a major shift toward earlier surgical intervention in macular pucker, Dr. McCannel certainly makes a strong argument in its favor.
Management of Complications Correlated with the Use of Intraocular Tamponade
In the following presentation, Grazia Pertile, MD, of the Sacrocuore Hospital, Negrar-Verona, in Italy, discussed complications related to the use of intraocular tamponade agents, particularly silicone oil, and reviewed methods to manage these complications. These are briefly summarized below:
– Suprachoroidal silicone oil – This is a rare, but potentially severe complication. In this scenario, the tip of the cannula is no longer visualized in the vitreous cavity during oil infusion, and has slipped into the suprachoroidal space. Dr. Pertile suggests first trying to free the tip of the cannula from the overlying choroid and replacing it within the vitreous cavity. If this is unsuccessful, the cannula can be kept in the suprachoroidal space and oriented tangentially to the sclera, prior to removing the silicone oil from the suprachoroidal space using the oil cannula in aspiration mode. It may also be beneficial to place a BSS infusion through one of the other cannulas to maintain pressure during oil removal.
– Subretinal silicone oil – This is a much more frequently encountered complication. A thin cannula can be passed through the existing retinal break and aspirated with a slow aspiration rate, while ensuring the cannula remains within the silicone oil bubble. However, more commonly, subretinal silicone oil is often encountered in the setting of extensive tractional membranes and the first step that is often necessary is the removal of preretinal (or subretinal) membranes. Often times, a relaxing retinectomy is also required in these patients and after creation of the relaxing retinectomy, the subretinal oil is often more easily liberated.
– Silicone oil in the anterior chamber – A small silicone oil bubble can be easily identified in the anterior chamber, but silicone oil filling the entire anterior chamber can be more difficult to identify (because a meniscus is not seen). In this situation, glistenings on the surface of the iris can be a useful indicator of the presence of silicone oil in the anterior chamber; this is seen particularly well upon angulation of the microscope light source.
– High intraocular pressure (IOP) and aphakia in the setting of intraocular silicone oil – Make sure your iridectomy is patent. If a patent iridectomy is already present, there may be a silicone oil overfill, and silicone oil may need to be removed.
– High IOP in the presence of a stable lens (pseudophakia/phakia) – One may need to remove silicone oil as there may be an overfill. The surgeon can further consider partially replacing oil with dispersive viscoelastic so as to prevent an oil overfill.
– Normal IOP and aphakia – Make sure a patent iridectomy is present.
– Normal IOP in the presence of a stable lens (pseudophakia/phakia) – No iridectomy is needed.
– Low IOP and aphakia – Make sure a patent iridectomy is present.
– Low IOP + phakia/pseudophakia – Cohesive viscoelastic may be used within the vitreous cavity to help regulate IOP in the setting of low aqueous production.
– Iridectomy location – In most cases, an iridectomy should be created inferiorly; however, if heavy silicone oil is used, then the iridectomy should be created superiorly.
Vitrectomy for Diabetic Macular Edema: Why, How, and When
Gaurav Shah, MD, of the Retina Institute of St. Louis, presented the subsequent talk on surgical interventions for diabetic macular edema, and presented a number of arguments in favor of various approaches, as well as on imaging-based pre-surgical evaluation.
In regard to vitrectomy for diabetic macular edema in general, there are physiologic several reasons we often see a benefit: 1) the elimination of clinical / sub clinical traction not visible with conventional means, 2) the removal of pathologic vitreous with inflammatory mediators (which favors the persistence of edema), and 3) increased oxygenation of inner retinal layers.
Dr. Shah then discussed factors that ought to be considered by vitreoretinal surgeons when assessing whether a patient may benefit from vitrectomy for diabetic macular edema. He began by summarizing the peer-reviewed literature on vitrectomy surgery for diabetic macular edema and showed that if vitrectomy is undertaken, internal limiting membrane (ILM) peeling is advisable as ILM peeling has been shown to benefit these patients in terms of effectively decreasing CSFT. Pathologic ILM has been demonstrated in previous studies: ILM has been shown to be approx. 2x thicker in diabetic eyes. Collectively, there have been 37 studies describing outcomes of vitrectomy for DME, which included pre and postoperative OCT measurements (both prospective and retrospective).
Aggregately, the literature has shown that the retina thins post-operatively without significant visual improvement; this may be because poor candidates were being chosen for surgical intervention based on time-domain OCT findings. At the time the majority of these studies were completed, spectral-domain OCT (SD-OCT) was not available; DRCR’s Protocol D was guilty of this as well.
Dr. Shah suggested that vitreoretinal surgeons ought to assess pre-operative and post-operative parameters on OCT more carefully when assessing whether a patient may benefit from vitrectomy for diabetic macular edema as these parameters may serve as valuable surrogate biomarkers of visual acuity and visual prognosis. These parameters include:
- the integrity of the external limiting membrane and ellipsoid zone,
- intraretinal hyperreflective foci (especially in outer retina; representative of lipoproteins or lipid-laden macrophages that damage ELM),
- disorganization of the retinal inner layers (DRIL), and
- macular ischemia (within deep plexus) or enlarged foveal avascular zone as detected by optical coherence tomography angiography (OCT-A).
We know from previous studies that DRIL can independently predict resolution of edema and visual acuity, and this needs to be taken into account accordingly. Another parameter mentioned is parallelism in which the degree to which the various retinal layers remain parallel to one another can be quantified, with the concept being that increased deviation from a parallel morphology would predict worse visual function.
The remainder of the discussion was used to review the findings of a study conducted by our Japanese colleagues, in which the response of a number of different OCT-based DME morphologies was examined. The morphological phenotypes described included
Diffuse retinal thickening with –
- sponge like diffuse retinal thickening (SDRT) – 35% – antiVEGF worked best
- cystoid macular edema (CME) – 24% – triamcinolone worked best
- serous retinal detachment (SRD) – 16% – vitrectomy seemed helpful
- all three (FULL)
When looking at the differential response rates of these subtypes of DME to either intra-vitreal triamcinolone, intra-vitreal bevacizumab, and vitrectomy, the results were as follows:
Triamcinolone – CME > SDRT > FULL > SRD (Those with CME-type DME were most responsive to triamcinolone)
Bevacizumab – SDRT > FULL > CME > SRD (Those with SDRT-type DME were most responsive to bevacizumab)
Vitrectomy – SRD > FULL > CME > SDRT (Those with SRD-type DME were most responsive to vitrectomy)
To conclude our first surgical session, Ramin Tadayoni, MD, PhD, of the University of Paris-Sorbonne, presented arguments in favor of earlier surgical intervention in eyes with myopic foveoschisis.
Myopic foveoschisis, a complication of high myopia is present in 10-30% of high myopia.
Also referred to in previous literature as retinal detachment of the posterior pole without a hole, foveal retinoschisis, or myopic traction maculopathy, myopic retinoschisis is thought to be due to retinal stretching between the pathologically growing sclera and relatively inflexible inner retinal layers in high myopia, although the mechanism is not completely understood.
Dr. Tadayoni continued by sharing that myopic foveoschisis is more common in high myopes with a refractive error greater than -6.0 diopters, an axial length greater or equal to 27mm, and in those with a posterior staphyloma involving the macula. While many patients may be asymptomatic, others may have variable degrees of vision loss. Metamorphopsia and scotoma are uncommon symptoms, except in the setting of concomitant macular hole.
The diagnosis is typically made by OCT: signs include thickening of the fovea, and macular stretching with non-reflective, column-like spaces in Henle’s layer.
In regard to additional OCT findings, the vitreous is attached in more than 85% of patients and an epiretinal membrane may or may not be present. Overall, the anatomy and visual function correlation is weak and therefore the OCT morphology alone may not be the sole predictor of visual function. To determine which patients might benefit most from vitrectomy for myopic foveoschisis, Dr. Tadayoni shared the results of a study of 66 eyes that underwent surgery for myopic foveoschisis. His results suggested that the only independent factor correlated with final best-corrected visual acuity was pre-operative visual acuity. He found that only in those with pre-operative visual acuity of better than or equal to 20/50 (with a mean of 20/40) was the final visual acuity better than 20/40. Whereas, those with worse pre-operative visual acuity were not able to achieve this final visual acuity outcome (better than 20/40). Based on these findings, Dr. Tadayoni raised the possibility that we may need to intervene when the visual acuity is 20/50 or better in order to achieve better final visual acuity outcomes.
However, the potential risks must be weighed when intervening: 10.6% lost vision post-operatively (3 mac holes, 1 posterior pole RD); interestingly, all of these occurred within the lowest visual acuity quartile in the study.