APVRS 2022 – Taipei, Taiwan – Issue 2

A Spirited Kickof f

The 15th APVRS Congress opens with a traditional ceremony

With a rousing tribal performance graced with blessings for all eye doctors and participants, the 15th APVRS Congress in conjunction with the 63rd Annual Meeting of the Chinese Taipei Ophthalmological Society (TOS) officially opened yesterday — marking the end of a three-year pandemic hiatus.

This year’s much-anticipated Congress marks APVRS’ first physical conference since the pandemic, welcoming over 870 delegates. It also comes immediately after Chinese Taipei’s strict COVID-19 measures had been finally lifted as a major step in its recovery plan to open the country for visitors.

A spirited show kicked off the ceremony with the famed local tribal music and percussions ensemble, Amis Kakeng Musical Group, giving a heartfelt performance using the Amis tribe’s “bamboo bells”.

by Joanna Lee

Prof. Chi-Chun Lai, president of the 15th APVRS Congress and president of the APVRS, welcomed all congress delegates during the opening ceremony.

Known as “kakeng” — for which the group is named after, the bamboo bells, traditionally used in weddings to usher in happiness, were featured along with the lead singer’s lyrics of well-wishes for the entire conference. The Amis tribe is Chinese Taipei’s largest indigenous group with over 200,000 members.

An outpouring of warm welcome and gratitude

Prof. Chi-Chun Lai, president of the 15th APVRS Congress, welcomed all Congress delegates. “Entering year three of the pandemic, I’m delighted that Taipei is the first to host the APVRS Congress which allows colleagues to reconnect and network with one another face to face again. We are so happy,” he beamed.

He also added a special note of gratitude to the Scientific Committee, especially Scientific Committee Chair Dr. Paisan Ruamviboonsuk and Co-Chair Dr. Wei-Chi Wu as well as APVRS Secretary General Dr. Andrew Chang, for making this Congress a success.

Prof. Lai also acknowledged the challenges that many international delegates faced especially with regard to securing visas while making their way to the Congress.

Meanwhile, Prof. Jiann-Torng Chen, president of Chinese Taipei Ophthalmological Society (TOS), also expressed his warm welcome to all delegates at the opening ceremony. “The Society is pleased to design a comprehensive program from the advanced researches to clinical discussions,” he expressed.

Of eye care collaborations and camaraderie

Ms. Eu Jin Liu, Medical Affair deputy director-general of the country’s Ministry of Health, also graced the ceremony. “Through this conference, we hope to take advantage of the developmental trends of ophthalmology in the world and enhance the treatment of ophthalmology,” she said.

She also emphasized the role of ophthalmologists in collaborating with optometrists to help the youth and disadvantaged groups in Chinese Taipei. “In response to the increasing medical demands for age-related vision problems in Asian societies, ophthalmologists play an important role in vision protection for the elderly.”

Another distinguished guest of honor, Dr. Tai-Yuan Cho, the immediate past president of the Confederation of Medical Association in Asia and Oceania, also gave a few words. “I’m thrilled to see all great medical professional minds gather under the same roof,” he said.

“I am delighted to see smiles and hugs as the delegates greet each other in person here. We enjoy the physical interaction while also interacting with our colleagues virtually,” enthused Prof. Andrew Chang, secretary general of APVRS.

Ending his speech on a positive note, Prof. Chang said: “They can’t put us down. Humans will always find a way. Congratulations to us all.”

The Constable Lecture

The APVRS’ opening ceremony also traditionally includes the Constable Lecture and the International Award Lecture

The APVRS Constable Lecture was established in 2016 in honor of Prof. Ian Constable, APVRS’ past president. The Constable Lecture awards individuals of 45 years old or below for outstanding contributions in advancing the understanding, diagnosis, and treatment of vitreoretinal diseases.

This year’s APVRS Constable Lecture Awardee is Dr. Tso-Ting Lai, who shared his findings in his lecture entitled Lamellar Macular Hole and Epiretinal Proliferations: Classifications and Clinical Implications. His lecture highlighted the clinical implications of the epiretinal proliferations (EP) which help indicate epiretinal membrane (ERM) induced Full-Thickness Macular Hole (FTMH) besides pointing to more severe disease progression.

“It is important to differentiate EP from ERM, whereby FTMH with EP should be diagnosed as ERM-induced FTMH,” he said. In high myopia, the lamellar macular hole with EP is protective against structural worsening. He also shared how important it is to preserve the EP whether by using the EP-sparing or EP-embedding methods.

Both methods were found to be effective even as the preservation of the EP can help to prevent complications and facilitate hole closure. Dr. Lai’s lecture was based on his studies in the past few years with some updates in the literature.

The APVRS International Awards Lecture

Finally, the Opening Ceremony also included the APVRS International Award Lecture, which was established in 2017 in honor of individuals from beyond the Asia-Pacific region, with no age restrictions.

This year’s International Award Lecture Awardee is Prof. Dr. Martine Jager, an immunologist from the University of Leiden in the Netherlands. Her keynote lecture, Collaboration or competition: Inflammation in COVID, Herpes Zoster and Uveal Melanoma, is based on her studies on the body’s immune system in relation to the abovementioned diseases.

Her laboratory in Leiden studied studied the role of the immune response (whether in collaboration versus in competition) in graft rejections in corneal transplantation, as well as observed the behavior of uveal melanoma to see if an immune response may prevent further tumor growth.

From her time working at the Bascom Palmer Eye Institute with Dr. Bruce Ksander in Miami, Florida, Dr. Jager learned to develop a uveal melanoma cell line, the 92.1. “We had also identified the gp100 as a well-expressed uveal melanoma antigen,” she shared.

She added that both the cell line and the gp100 have been used to develop the first treatment for uveal melanoma metastases by the company Immunocore in 2020 with positive results shown recently.

“We have sent the cell line all over the world, and it is now present and being used in Chinese Taipei,” Prof. Jager enthused.

Uveal melanoma, although low in incidence, is a malignant tumor in adults, presenting a high mortality risk of 50%. It spreads through the blood, giving rise to liver metastases. Patients usually die from metastases. “Till the development of this Immunocore against gp100, there was no treatment for the metastases,” she said.

She further showed how the high number of macrophages in tumor cells is associated with worse survival chances in uveal melanoma.

“The innate immune system as made up of antigen-presenting cells not only helps to develop the specific immune system, but also contributes to chronic inflammation and blood vessel formation,” she said, closing her lecture with a challenge to researchers to continue publishing more studies based upon these findings.

Hot Button Topics

ILM peeling, scleral buckle, endophthalmitis, and other controversial issues and innovations in surgical retina

by Tan Sher Lynn

With complications and controversies surrounding internal limiting membrane (ILM) peeling, is it really necessary to do so?

This and other controversies and innovations in surgical retina were among the highlights and issues tackled on Day 1 of the 15th Asia-Pacific Vitreoretina Society (APVRS) Congress, as retinal surgeons presented the latest ideas and progress in vitreous surgery and the pathology of vitreoretinal diseases.

To peel or not to peel

ILM peeling has been proposed as a method used to prevent epiretinal membrane (ERM) formation in eyes that have undergone vitrectomy for rhegmatogenous retinal detachment (RRD). However, ILM peeling may cause retinal damage during surgery and delay visual recovery. It is also difficult to peel the ILM in eyes with maculaoff RRD complicated by proliferative vitreoretinopathy (PVR).

Hence, “is ILM peeling necessary to do so?” — asked Dr. Shumpei Obata from Japan.

Using prospective data from the JapanRetinal Detachment Registry, Dr. Obata and his colleagues compared the anatomical outcomes and visual acuity (VA) changes between eyes with ILM peeling and eyes without ILM peeling on subjects who had macula-off RRD complicated by PVR.

They found that removal of ERM was unnecessary in all eyes with ILM

peeling, while it was necessary in 3% of eyes without ILM peeling. Meanwhile, preoperative VA and younger patient age were significantly associated with poor postoperative VA at 6 months. However, ILM was not associated with poor VA.

They also looked at previous studies that showed controversies regarding the effect of ILM peeling on the anatomical outcome.

“ILM peeling does not have a clear beneficial effect in anatomical and functional outcomes, and it might be unnecessary for macula-off RRD complicated by PVR,” shared Dr. Obata.

Scleral buckle vs. pars plana vitrectomy

There are many ways to fix retinal detachment, such as scleral buckle, pars plana vitrectomy, and pneumatic retinopexy.

When it comes to choosing the right procedure for the patient, Dr. Wong Jun Shyan from Malaysia said that the safety, efficacy, simplicity, and costeffectiveness of the procedure should be taken into consideration.

“Scleral buckle can be done with minimal high-tech instruments, is particularly useful in simple retinal detachment in young patients with no (or incomplete) posterior vitreous detachment (PVD), does not require posturing, is without air travel restrictions, and is especially good in inferior detachment with PVR<grade B. But it is technically demanding, and is less frequently taught in training programs nowadays,” Dr. Wong explained.

On the other hand, vitrectomy allows the elimination of vitreous traction, removal of media opacities, better visualization of breaks, and controlled internal drainage of subretinal fluid. There should be no worries over problems related to

external drainage, hemorrhage, retinal incarceration, and others. There are also minimal risk of diplopia from buckle element, minimal distortion of globe and astigmatism, as well as less morbidity compared to scleral buckle.

“Both techniques are important in retinal detachment (RD) repair, and the decision to choose which procedure [to use] is influenced by patient and surgeon factors,” continued Dr. Wong.

“Final reattachment outcomes are similar in both procedures, while single operation success tends to be slightly higher in PPV. The visual quality of the procedures is not fully addressed in literature. Nevertheless, vitrectomy is now the mainstay of RD repair in 2022,” he concluded.

Endophthalmitis trends and complications

Acute endophthalmitis can cause severe devastating complications. “We used to see endophthalmitis complications in post-cataract cases, but following the exponential rise of intravitreal injections (IVI), we are seeing more and more of them nowadays,” said Dr. Andrew Chang from Australia, noting that the risk of endophthalmitis is 0.008% to 0.092% following IVI and 0.03% to 0.7% following cataract surgery.

According to him, the condition can be due to patient-related factors (such as patient’s own flora [67%-82% bacterial isolates on conjunctiva]), procedurerelated factors (unplanned anterior vitrectomy, which increases the risk 10 times), or surgeon-related factors (poor sterile technique).

Wanting to explore the difference in outcomes between endophthalmitis following cataract surgery and IVI, Dr. Chang and his colleagues examined 101 eyes in 101 patients with acute endophthalmitis (53 post-IVI, 48 postcataract surgery) at the Sydney Hospital, and found that post-IVI endophthalmitis had poor outcomes, with increased Streptococcus infection (24.53% vs. 6.25%).

They also examined the changing spectrum of endophthalmitis in the Sydney Hospital and found that there were less Streptococcus cases (although they were still common), probably due to

the use of masks and reduced talking.

Meanwhile, through the Sydney Eye Hospital Early Vitrectomy Study, they found that culture-negative endophthalmitis and post-cataract surgery endophthalmitis were associated with better visual outcomes.

In terms of technology, Dr. Chang noted that micro-incisional vitrectomy is effective in improving vision in acute infective endophthalmitis. “With changes in technology and patient presentation, we should review the Endophthalmitis Vitrectomy Study (EVS),” he said.

Lutein supplement for RD

While surgery for RD is effective in reattaching the retina, it may not restore vision. Merely less than one-third of macula-off RD could achieve good vision (6/12 or better) after surgery.

“Since vision loss related to maculaoff RD is primarily due to apoptosis of retinal photoreceptors, neuroprotective therapy may prevent apoptosis and thus improve visual outcome,” noted Dr. Danny Cheung from Singapore.

Lutein is a well-known neuroprotecitve agent for RD due to its blue-light-filtering and anti-inflammatory properties. Having proven that lutein reduces photoreceptor apoptosis in rats with RD, Dr. Cheung

They carried out the Lutein as a Novel Neuroprotective Adjunctive Therapy to Improve Visual Outcome of Retinal Detachment (LUNAR) Study, which is a prospective, randomized, doublemasked, placebo-controlled clinical trial.

The study drug contained 20 mg lutein, 1 mg zeaxanthin, and inactive ingredients; while the placebo contained inactive ingredients only. The treatment group took lutein upon enrolment, and RD surgery was performed within one week. Only patients with primary maculaoff RD are included.

Results show that on average, the lutein group had better VA than the placebo group (by about 1.5-line or 10 ETDRS letters) at 6-week (23.3% vs 10.3%) and 12-week (18.6% vs. 12.8%) visits. The lutein group also consistently showed high macular sensitivity across a 12-month period.

Dr. Cheung shared that oral lutein supplement may improve visual outcome after surgery for primary macula-off retinal detachment.

“Beneficial effects are most prominent during the early to mid-phase of postoperative recovery, suggesting that lutein may promote faster recovery of visual function. However, a larger study may be warranted to verify our results, and to determine if any specific subgroup or type of patients would benefit the most from lutein supplement after surgery,” he concluded.

Diabetes in Focus

Getting to the root of diabetic eye diseases

It’s a well-known fact that diabetes is a global epidemic, highlighted Dr. Rajiv Raman from India, as he opened the Diabetic Retinopathy Symposium on Day 1 of the 15th Congress of the Asia-Pacific Vitreo-retina Society (APVRS 2022).

Today, one in 10 people has diabetes and in 2045, it is projected to be one in eight, reported Dr. Raman. “An alarming figure, indeed… and what is troubling is that half of the people with diabetes

by Gloria D. Gamat

don’t know that they have it. In most cases, the condition is undetected. Moreover, almost half of the people with diabetes are from these three countries: China, India, USA,” shared Dr. Raman.

Diabetes is a condition of critical importance in ophthalmology, it’s a precursor to important serious eye conditions, most especially diabetic retinopathy (DR) and diabetic macular edema (DME). During the session, global experts dissected the current tools and

therapies available and got to the root of how to best manage these diabetic eye diseases.

For example, an important problem in Asia-Pacific, diabetic retinopathy, in the last few years, has seen a lot of changes. Not only are (new) pathways understood better now, but there are also improvements in pharmacotherapy and huge developments in surgical armamentarium.

Below are some of the highlights of the symposium.

Faricimab vs. DME in Asian patients

Speaking about new pharmacotherapies, Dr. Susumu

Ishida from Japan talked about a relatively new drug, faricimab, that is under observation in Asian DME patients.

Faricimab is the first intraocular bispecific antibody inhibiting Ang-2 and VEGF-A — one molecule with two disease pathway targets for durable efficacy. He presented results from a one-year subgroup analysis of the Phase 3 YOSEMITE and RHINE trials — two major studies that investigated the efficacy, safety, and durability of faricimab compared with aflibercept in patients with DME.

Published data of the studies’ results suggest that robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks (q16w) in more than 70% of patients. Such findings demonstrate the potential for faricimab to extend the durability of treatment for patients with DME.

Further, Dr. Ishida emphasized that the results in Asian groups are consistent with results in non-Asian groups. “Unlike age-related macular degeneration, DME behaves similarly worldwide… similar in various patient population groups,” he shared.

Diabetic retinopathy in uveitis — what’s the relationship?

“When uveitis and DR are in the same space, what happens to each other?” asked Dr. S. Sudharshan from Chennai, India, when he opened his session.

Diabetic retinopathy, mentioned Dr. Sudharshan, was used to be called retinitis, probably because of the inflammatory factor of its pathogenesis.

Are diabetics more prone to uveitis, or does diabetes cause uveitis? Are uveitis patients more prone to diabetes and DR? Is uveitis protective of DR? Such were the questions he presented to the audience during this session.

“If it’s the cause, how does diabetes cause uveitis? The answer could be immunological… when diabetes is uncontrolled, it leads to immunosuppression. Uveitis is often associated with uncontrolled diabetes, it worsens diabetic retinopathy,” explained Dr. Sudharshan.

He added that the combination of both (uveitis and DR) is a “scary situation” and can lead to further ocular complications.

Novel OCT and OCT-A markers in DME

There are a lot in the armamentarium of biomarkers in diabetic macular edema, especially in terms of invasive and non-invasive biomarkers, reported Dr. Pradeep Susvar from Chennai, India.

Among these, the OCT and OCT-A biomarkers provide the retina specialist with a quantitative way to evaluate the edema. In literature, there is a wide range of biomarkers published — these are divided into two parts: biomarkers for functional and anatomical measurements.

As a retina specialist, noted Dr. Susvar, we have to look into how these OCT and OCT-A biomarkers influence the selection of eyes for clinical studies targeting DME.

“More importantly, keeping in mind these biomarkers, we can improve risk stratification and early detection, we can advance the clinical management, and we are able to substantially enhance patient counseling,” he summarized.

Novel concepts in the management of DME

DME is the most prevalent cause of visual impairment in patients with diabetes, Prof. Anat Loewenstein from Israel, reminded the audience. Its impact affects the patient’s quality of life similar to neovascular age-related macular degeneration (nAMD).

The treatment of these two has pretty much evolved similarly throughout the decades — from the “no treatment” in the 1980s to the huge breakthrough of anti-VEGF therapy in 2006. But it doesn’t stop there, emphasized Prof. Loewenstein. The evolution of anti-VEGF continues because experts are nowadays looking into optimizing the outcomes.

“Unfortunately, real-world evidence shows poor visual outcomes with a smaller number of injections, thus indicating undertreatment,” said Prof. Loewenstein. One of the reasons is that diabetic patients are non-adherent and non-compliant with their treatment — leading to significant vision loss as demonstrated by bad visual acuity results and persistent DME, explained Prof. Loewenstein.

Towards an optimized treatment management

In optimizing the outcomes, the goal is to have a treatment regimen that benefits the patients, physicians, and the healthcare system — a treatment option, according to Prof. Loewenstein, that provides maximal and sustained VA gains, improved disease control, faster fluid resolution, and fewer injections leading to longer treatment intervals. All that, she highlighted, involves investigating new pathways and mechanisms, including optimized anti-VEGF protocols, new pathways and molecules, and gene therapy.

“There are a lot of developments in DME. In terms of biomarkers, we have a lot of data that we don’t know which to use. There is a need to look beyond a single pathway anti-VEGF. Understanding the pathophysiology and looking at new pathways provide many opportunities and possibilities,” shared Prof. Tien-Yin Wong from Singapore, when asked to comment on the subject matter.

‘Trends’ to Watch

had their macular holes closed. When neither ILM peeling nor ILM flap was done, only two eyes had their macular holes closed.

Exciting techniques and findings in the vitreo-retinal field

For retina specialists, nothing piques the interest more than topics about complicated retinal diseases and novel approaches in treatment, surgery, and management. And the TRS/TMS Symposium, co-organized by the Taiwan Retinal Society and Taiwan Macula Society, certainly did not disappoint.

In this symposium, exciting topics in surgical and medical retina, including macular hole, retinal detachment, vitreomacular interface disease, familial exudative vitreoretinopathy, and Stargardt disease were discussed, to the delight of many eager attendees.

Here are some of the exciting industry ‘trends’ that may interest you.

Repairing RRD complicated with MH

Before the era of vitrectomy, rhegmatogenous retinal detachment

by Tan Sher Lynn

(RRD) was merely repaired with a scleral buckle, leaving the macular hole (MH) untreated, noted Dr. San-ni Chen from Chinese Taipei.

“Before the era of internal limiting membrane (ILM) peeling, MH closure rate is 31% while after ILM is widely used, MH closure rates increased to 73% to 90.7%,” she said, adding that the characteristics of MH coexisting with RRD include a less favorable visual outcome, higher incidence of reoperation, and higher incidence of PVR.

Dr. Chen and her colleagues did a retrospective comparative study of 40 eyes with MH coexistent with RRD, and 80 eyes with macular off RRD without coexisting MH.

In cases with macular hole retinal detachment (MHRD), ILM peeling was done on 19 eyes and 17 eyes had macular holes closed. Of 14 eyes that underwent a hinged single layer, 11 eyes

“Ellipsoid zone (EZ) lining at the bottom of MG is also often observed in RRD with MH. And different morphology of MH in optical coherence tomography (OCT) suggests different pathogenesis of MH,” Dr. Chen shared. She also observed a higher chance of CD, long duration of RD, high myopia, PVR, and large extent of RD in eyes with coexisting MH.

“Those eyes also have poor initial and final best-corrected visual acuity (BCVA). ILM peeling or ILM flap is necessary for macular hole closure,” she concluded.

Manipulation of ILM flaps with the SPOT technique

An ILM flap is generally recommended for MH that are larger than 400 μm. For smaller holes, it was previously believed that it was not necessary to have additional flaps since the primary success rate is approaching 100%.

“However, in our recent studies, we have found that using an additional ILM flap can achieve faster vision recovery compared to conventional ILM peel alone. Therefore, an additional ILM flap is still worth considering for smaller holes,” said Dr. Hung-Da Chou from Chinese Taipei.

But not all inverted flaps are created equal. For example, a single-layer flap

cover is better than a multilayer flap insertion.

Handling a flap is not easy for beginners and can sometimes be tough even for advanced surgeons. Flap dislocation is also not uncommon, having been reported to be as high as 14% to 20%.

To overcome these issues, Dr. Chou and his colleagues have developed the sub-perfluorocarbon ocular viscoelastic device (OVD) injection (SPOT) technique to stabilize the flap on the spot. This technique proved to be great for beginners, as well as in the handling of more complex flaps.

“The SPOT technique secures flaps perioperatively and postoperatively. A readily available and easy-to-learn technique for all levels of surgeons, it can be applied to various macula surgeries that require a flap,” Dr. Chou said.

Know what makes great ILM forceps

ILM removal is considered a useful surgical approach in different kinds of macula disease, including vitreomacular interface disease, decompression of macular edema in cases of diabetes and RVO, deroofing for subhyaloidal hemorrhage, and prevention of PVR membrane in RD, shared Dr. Yu-bai Chou from Chinese Taipei.

He noted that there are many techniques for ILM peeling, such as total ILM

peeling, ILM peeling with fovea sparing, and inverted ILM flap to help surgeons deal with different kinds of macular diseases. There are also plenty of different kinds of forceps for various ILM peeling techniques and thickness of membranes.

Most surgeons create the ILM flap using the “pinch and peel technique”. Hence, important characteristics of the ILM peeling instrument include the ability to create less pressure during a pinch, having high surgical precision to make the ILK edge efficiently, and providing a strong grasping force for manipulation of the ILM flap. These characteristics can lead to less unnecessary damage, greater control of the ILM, and shorter surgical time.

“In short, the innovative design of ILM forceps should provide less iatrogenic damage at IML peeling, surgical precision through the conforming platform, and better grasping ability to save surgical time,” Dr. Chou concluded.

Watch out: Predisposing factors to vitreomacular interface diseases

In a previous study, Dr. Yi-ting Hsieh from Chinese Taipei and his colleagues found that a wide-based foveal pit is associated with idiopathic epiretinal membrane (ERM), macular hole, and being female; as well as having a wide retinal artery trajectory (RAT), thin central foveal thickness (CFT), and large (foveal avascular zone) FAZ.

“We think that there may be a larger centrifugal tractional force on the macula which will result in a wider RAT, a wider foveal pit, and a thinner foveal thickness. Such force may eventually result in ILK clefts (which will result in glial cell proliferation and ERM formation) and macular hole formation,” explained Dr. Hsieh.

To confirm their suspicion, they did a cross-sectional study comparing the foveal pit width and retinal artery trajectory between fellow eyes of unilateral idiopathic ERM versus control, and fellow eyes of unilateral macular hole versus normal controls, under the hypothesis that the macular structures of both eyes of the same subject should be similar before the formation of ERM or MH.

Results show that not only do the fellow eyes of ERM have larger foveal base width (FBW), but the FAZ is also larger and the RAT is wider, and females have wider foveal base width and RAT than males. FBW and RAT are also larger in fellow eyes of macular holes.

“These findings support our proposal that some centrifugal tractional force may exist on the macula of eyes with a wide-based foveal pit and a wide RAT, which eventually may result in the formation of idiopathic ERM due to glial cell proliferation from the ILM clefts. Both wide-based foveal pit and wide retinal artery trajectory are potential biomarkers for vitreomacular interface diseases, including ERM and macular hole,” explained Dr. Hsieh.