Olufemi Adams, MD and Michael Yu, MD
Wills Eye Hospital, Philadelphia, PA
During this year’s Debates at Retina Subspecialty Day, experts sparred over medical and surgical retina topics ranging from the use of complement inhibitors for geographic atrophy to the timing of surgery for macula-involving rhegmatogenous retinal detachments. Moderated by Dr. Sunir Garg (Wills Eye Hospital), the session was both informative and engaging. The audience were asked to vote at the conclusion of each debate on whichever side made the more convincing argument.
Complement Inhibitors for the Treatment of Geographic Atrophy
Pro: Dr. Anat Loewenstein (Tel Aviv Medical Center) started off by arguing in favor of complement inhibitors to treat geographic atrophy. She focused on the functional burden of geographic atrophy, mentioning how two-thirds of patients diagnosed with geographic atrophy lose the ability to drive within 2 years. Dr. Loewenstein argued that while clinical trials often focus on visual acuity, visual function is actually a more meaningful metric, and likely does not capture the full potential benefit of complement inhibitors. What we do know from trials thus far is that pegcetacoplan causes up to a 42% decrease in GA growth with increasing effect over time and while visual acuity benefits were minimal, quality of life metrics were improved. Dr. Loewenstein noted that microperimetry results demonstrated a benefit with pegcetacoplan at a 3-year pre-specified end-point, suggesting that the preserved tissue is functional. Additionally, she preempted concerns about risks of complement inhibitor use, by stating that most known adverse effects are manageable. She concluded by emphasizing the importance of slowing GA growth, making a compelling emotional appeal for older adults to cherish time with their grandchildren.
Con: Dr. Demetrios Vavvas (Mass Eye and Ear Infirmary) argued against the use of complement inhibitors for geographic atrophy, expressing significant skepticism regarding their functional benefits. He bluntly countered that these drugs 1) fail to improve vision for patients, 2) fail to prevent vision loss, and 3) can cause progression (through development of CNV) to two advanced stages of disease, rather than just one. To support these claims, Dr. Vavvas presented data which showed that visual acuity, microperimetry, reading speed, and independence declined with these treatments. He also cited data from the FILLY and OAKS/DERBY clinical trials, which showed that patients who developed neovascular AMD as a result of complement inhibition experienced significantly worsened vision compared to patients with existing neovascular AMD. He concluded that a treatment offering minimal or no functional benefit, coupled with significant risks, imposes an additional burden on patients who are already facing the considerable challenges of GA. His assertions deeply resonated with the audience, ultimately resulting in 82% of attendees voting against the use of complement inhibition for GA.
The Role of Fluorescein Angiography in Wet AMD:
Pro: Dr. Jose Pulido (Wills Eye Hospital) argued in favor of obtaining an initial fluorescein angiography for all patients diagnosed with neovascular AMD. Dr. Pulido presented the case of a 57-year-old patient with a diagnosis of presumed AMD, where fluorescein angiography identified subclinical angioid streaks. This finding fortunately led to a diagnosis of pseudoxanthoma elasticum, which, he explained has significant systemic implications, including possible death from gastrointestinal or cardiovascular hemorrhages. Without fluorescein angiography, this person’s subtle findings may have gone unnoticed. He concluded that fluorescein angiography provides a different perspective, allowing clinicians to see the forest through the trees.
Con: Dr. Dave Brown (Retina Consultants of Texas) presented a compelling counterargument, asserting that classic findings on imaging modalities such as OCT do not require additional validation on fluorescein angiography due to significant associated risks. Most notable, he mentioned, is the risk of death, which is 1 in 220,000 (the serious adverse event rate is greater, at 1 in 1900). He also cited studies showing that the sensitivity and specificity of FA is equivalent to OCT and that, moreover, FA does not alter the initial clinical management of neovascular AMD. He pointed out that FA also introduces significant overhead costs, which could result in a net loss for practices. He concluded by stating, “If it looks like a duck, walks like a duck, and quacks like a duck, it’s probably a duck”; if OCT depicts a typical CNV in the setting of AMD, there is no reason to suspect it is anything else.
Pneumatic Retinopexy:
Pro: Dr. Rajeev Muni (University of Toronto) advocated for the use of pneumatic retinopexy to repair simple rhegmatogenous retinal detachment with a single superior retinal break. He presented a variety of data including from Dr. Tornambe, which depicted better visual acuity results with pneumatic retinopexy compared with scleral buckling. Additionally, the PIVOT (Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes randomized trial) compared pneumatic retinopexy to vitrectomy, and demonstrated better functional outcomes, lower rates of vertical metamorphopsia and retinal displacement, as well as improved EZ and ELM discontinuity compared with PPV. He also reported findings from ALIGN, a multicentered non-randomized comparative prospective clinical trial which demonstrated that vitrectomy carried an increased risk of retinal displacement and aniseikonia. Outer retinal folds, a poor prognostic imaging biomarker, were worse with vitrectomy compared to retinal reattachment with pneumatic retinopexy. Dr. Muni argued that there is no reason to subject patients to worse outcomes and other complications, including cataract formation, when pneumatic retinopexy is available.
Con: Dr. Michael Altaweek (University of Wisconsin) countered by pointing out the downsides to pneumatic retinopexy. First, he mentioned that PIVOT likely significantly overstates the success of pneumatic retinopexy; he mentioned that the inclusion and exclusion criteria used in PIVOT are likely not generalizable and that as such, the real-world success of pneumatic retinopexy is likely much worse. Failure rates and subsequent development of new tears with pneumatic retinopexy were higher compared to vitrectomy in all meta-analyses and in the IRIS registry analyses, which demonstrated a single operative success rate of 68.5% with pneumatic retinopexy compared to the PIVOT trial. Earlier, Dr. Muni described that outer retinal folds are initially more common with vitrectomy, but Dr. Altaweek countered that at 6 months, these rates become equal and low in both groups, and the distortion can decrease over time. Additionally, while the pneumatic groups start with better visual acuity and end with better visual acuity, there is overall better improvement in visual acuity with PPV. Although pneumatic retinopexy is appropriate if the right conditions are met, due to an expansion of its utility beyond the original indications, vitrectomy and/or scleral buckle remains the optimal first choice for repairing most retinal detachments.
Timing of Surgery for Macula-Off Retinal Detachments:
EARLIER: Dr. Tarek Hassan (Beaumont Health/Associated Retinal Consultants) argued for earlier surgical intervention in cases of macula-off retinal detachments. He stated, “when arguing the OBVIOUS, one must defend against the ABSURD from my opponent”, and characterized the opposing argument as a formal technique of science denial, likening it to the “Flat Earth Society”.
Dr. Hassan argued that common sense dictates earlier surgical intervention, and that there is frankly no situation in which later surgical intervention is ever a better idea. If the macula or fovea are at risk, then earlier intervention could prevent future vision loss. If the macula is already detached, earlier repair could restore vision. He cited studies that showed photoreceptor death which starts at 12 hours and peaks at 3 days; given that it is impossible to know the true duration of a retinal detachment based on patient report alone, sooner intervention makes the most sense. While older literature showed that repair within 7 days was sufficient, most of these involved scleral buckling, which left residual subretinal fluid in the macula and likely affected long-term visual prognosis; with modern approaches that often include vitrectomy, the issue of residual subretinal fluid is mitigated and with it, long-term visual prognosis is likely better with sooner repair.
LATER: Dr. Carl Awh (Tennessee Retina) creatively argued the opposing view, emphasizing that instead of taking patients “early,” we should take them at the “appropriate” time. He stated that the word “early” implies “before the usual and expected time,” and thus, in the context of macula-off retinal detachments, the definition of early surgery is unclear.
Further, Dr. Awh jokingly mentioned that when deciding the timing of surgery, “we should not make statements that could come back to haunt us.” He highlighted that the question of whether surgery should have been performed earlier typically arises only when outcomes are disappointing, and patients and lawyers focus on these questions. As a point of tact, he raised a compelling point that professional society guidelines, videos and presentations at major medical meetings may be considered authoritative in legal action, and cautioned the audience to vote no against this blanket statement, asserting that “public pronouncements carry consequences”. He concluded that macula-off retinal detachments should be repaired at the appropriate time, which should be determined by each surgeon and patient, rather than an earlier time, which is vague.
A slide from Dr. Awh’s counterpoint.
Vitrectomy for floaters:
PRO: Dr. John Kitchen (Retina Associates of Kentucky) argued in favor of vitrectomy for floaters. He prefaced his points by stating that vitrectomy for floaters is one of the most common surgeries he performs. Floaters, he argued, are particularly bothersome to some patients and can be remedied with a simple, safe, and effective surgery. While we often assess how symptomatic patients are based on their best-corrected visual acuity, patient symptoms often transcend BCVA. To support this claim, Dr. Kitchen presented studies which showed decreased contrast sensitivity in patients with symptomatic vitreous opacities.
Dr. Kitchen also argued the cost-effectiveness of vitrectomy for floaters, and showed that these surgeries achieve $1,500/quality adjusted life year (QALY), which surpasses that of even cataract. While cataracts are a risk, he stated, everyone develops cataracts. More serious adverse effects, like retinal detachments, occur less frequently, at 2.6%, which he argued was an acceptable risk-profile.
CON: Dr. Kevin Blinder (Washington University at The Retina Institute) argued the counterpoint by emphasizing the risks associated with the surgery. While vitrectomy is safe, he argued, it is not risk-free. Moreover, the symptomatic patient may not be symptomatic forever and thus, patients may benefit from a more conservative means of self-resolving symptoms.
Dr. Blinder showed data from Rubino et al (Ophthalmology Retina, 2020) showed that of 17,000 eyes which underwent vitrectomy for vitreous opacities, a significant portion required return to the operating room for one reason or another: 12.4% required cataract surgery, 2.6% for retinal detachment repair, and 3.7% for non-cataract and non-RD surgical intervention. Newer data of over 42,000 eyes undergoing vitrectomy showed additional risks of vitreous hemorrhage (26.3%), retinal detachment (4.2%), and endophthalmitis (3.7%). Vitrectomy for vitreous opacities is a serious surgery, he argued, and should be performed with careful consideration.
As always, the debates were entertaining and educational. We’re already looking forward to next year’s!