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Sophisticated programmes require an evolving mindset

Balancing the promises  and challenges of artificial intelligence

Over the last 15 years, biosimilars have become a major feature of the health care landscape. Physicians in many disciplines, particularly oncology and immunology, have embraced biosimilars. However, access to educational resources on these powerful biologics can be inconsistent, and in turn, some ophthalmologists who could benefit from the adoption of biosimilars are left in the dark.

The real-world application of biosimilars was the focus of discussion for Martin Zinkernagel, MD, PhD, chair of the Department of Ophthalmology at the University Hospital of Bern, Switzerland, and Paolo Lanzetta, MD, professor of ophthalmology and chairman of the Department of Medicine-Ophthalmology at the University of Udine in Italy. In their discussion, the experts addressed several common questions, framed around the phase 3 clinical trial for biosimilar SB11 (BYOOVIZ) from Biogen. SB11 is approved in Europe and the United Kingdom. Like the reference product ranibizumab (Lucentis), SB11 is approved for the treatment of retinal disease including neovascular age-related macular degeneration (nAMD).

Addressing physicians’ levels of familiarity with biosimilars, Dr Lanzetta attributed much of the variation to regulatory discrepancies. “The uptake of biosimilars varies throughout Europe by country and by product,” he said. “Obviously, variation in the uptake of biosimilars [is] influenced by government involvement, reimbursement issues and tender procurement policies.” Recent survey data have revealed gaps in awareness across Europe and in the United States on the efficacy and safety of biosimilars for retinal diseases, Dr Lanzetta said, especially in terms of “real-world data.”

In a clinical application, Dr Lanzetta said, biosimilars may exhibit minor differences from the reference products, but they aren’t considered to have significant impact on the efficacy or safety profile. Typically, the biosimilar and reference medicine must have the same posology and route of administration, with few exceptions, he added.

Dr Lanzetta also said that in the last 10 years, the European Medicines Agency (EMA) has approved the highest number of biosimilars worldwide.

 “And this means, to us physicians, having both the possibility to have experience on their use in terms of safety and evaluating the efficacy after that,” he explained.

One common misconception about biosimilars is that these therapeutics are interchangeable with the idea of generic medicines. But there is a key indicator that biosimilars are unique: the cost. “While generic medicines are marketed at a significantly lower price than name brand ones, why do we not see the same level of cost savings with biosimilars?” Dr Zinkernagel asked.

Dr Lanzetta explained that biosimilars are developed via a rigorous, complex and highly regulated manufacturing process. “Generics are simple chemical medicines or agents, which is not the case for biosimilars and biologics,” he said. “Unlike generics, biologics, and therefore biosimilars as well, are very complex; they’re very difficult to copy. And the development processes are patented and proprietary to the originators.” The proprietary nature of biologic development, he added, is why biosimilars may have differences from their originators.

Prof Zinkernagel and Dr Lanzetta used data from the SB11 phase 3 trial to expand upon the capabilities of biosimilars. Prof Zinkernagel detailed the study: over 700 patients were included in the randomised, double-masked, parallel-group multicentre trial. Over 52 weeks, investigators evaluated the efficacy and the safety profile of this biosimilar SB11 in comparison with monthly ranibizumab for the treatment of nAMD.

“Patients with neovascular AMD were included, [with a] visual acuity range between 20/40 and 20/200,” Prof Zinkernagel said. “[Patients] were randomised in a 1:1 ratio to either have the originator or the biosimilar every 4 weeks from baseline up to week 48.”

Primary end-points were change from baseline in best corrected visual acuity at week 8 and change from baseline in central subfield thickness at week 4. The pre-specified secondary efficacy end-points included longer-term assessments of change from baseline in visual acuity, and the proportion of participants who lost fewer than 15 letters or who gained 15 or more letters in visual acuity from baseline at weeks 24 and 52.

“Other secondary end-points included, of course, change from baseline in central subfield thickness and central retinal lesion thickness at week 24, as well as change from baseline in choroidal neovascularisation [CNV] size and proportion of participants with active CNV leakage seen via OCT [optical coherence tomography] at week 24,” Prof Zinkernagel continued. Describing the results, he said, “When you look at the visual acuity improvements, it’s really equivalent. You have equivalence between the originator and the biosimilar, and the same holds true for a decrease in central retinal thickness. So the curves are basically the same, and also the secondary end-points.”

Prof Zinkernagel also spoke about the immunogenicity outcomes of the SB11 trial, as immunogenicity reactions have been a common problem in past assessments of anti–vascular endothelial growth factor (VEGF) agents. Along with detrimental effects to visual acuity, immunogenicity reactions can also lead to vasculitis and vitritis.

“Now, in this trial, the overall cumulative incidence of anti-drug antibodies, antibodies reacting against this specific drug up to week 52, was very low,” Prof Zinkernagel said. “For the SB11 biosimilar, it was 4.2%, and for the originator it was 5.5%. So very, very similar.”

He also noted that most antibodies were non-neutralising, which generally indicates a weak antibody response. “Furthermore, no statistical or clinically relevant differences in the incidence of anti-drug antibodies and neutralising antibodies were observed between treatment groups at any of the time points,” Prof Zinkernagel explained.

Dr Lanzetta highlighted the unique potentialities for anti-VEGF therapies as an area where physicians can consider treating patients with a biosimilar. “You can either switch a patient from the originator, obviously, or you can also consider treating with a biosimilar treatment-naive patients who may benefit…from being treated with that reference agent or originator agent,” he said. When to deploy a biosimilar will depend on many factors, including the locality where a patient is being treated. “Europe has different countries, different health care systems,” Dr Lanzetta said. “You may consider treating with the biosimilar patients who may not be strictly adherent to the cost of therapy and the frequency of treatment because of some cost issues.”

Just as education on biosimilars is vital to practitioners, awareness and education resources for patients are vital, too. “We spend a lot of time with our patients in letting them know that biologics did undergo a very rigorous approval process through studies, efficacy and safety studies,” Dr Lanzetta emphasised. This education is vital to getting patients on board with biosimilars, and it sparks enthusiasm about the potential benefits. “Once they do understand that, I think they will be very prone to receive a biosimilar; [it’s] in their interest and in the interest of the community, the whole community of patients, and in the interest of the health care system,” Dr Lanzetta said.

1. Biosimilars in the EU: information guide for healthcare professionals. European Medicines Agency. Updated December 2, 2019. Accessed October 3, 2023. 

https://www.ema.europa.eu/en/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pd

Editor’s note: A prior version of this article contained a misspelling of the product name BYOOVIZ. It has been corrected. We regret the error.

How biosimilars expand treatment options for patients with retinal disease

As 2023 nears its end, the reporters and editors from the Eye Care Network would like to thank you–our readers–for engaging with our print magazine, eNewsletters and video interviews. Throughout the year, we have had the privilege of working alongside industry opinion leaders to showcase what’s new and what’s upcoming in the ophthalmology space. If 2023 has shown us anything, it is how much we have to look forward to in 2024 and beyond. From groundbreaking research to cutting-edge tech, there is plenty of reason for eye care professionals and their patients to be excited.

This week, you will see a series of posts featuring the best content from Eye Care Network brands. We’ll showcase our colleagues at 

, so keep your eyes peeled (and pardon the pun!).

To kick off our “year in review,” here are the 5 most important stories featured in Opthalmology Times Europe throughout 2023.

Is ophthalmology approaching the end of LASIK?


Jod Mehta, PhD, FRCOphth, who is the Distinguished Professor in Clinical Innovation in Ophthalmology at Singapore National Eye Centre, contributed this cover story for our September issue. The article was based on his 2023 British Society of Refractive Surgery Charles McGhee Lecture. Our editorial team was immediately captivated by the lecture title, “Lenticule Extraction: Will LASIK Cease to Exist?”

Prof Mehta explores that provocative question at length in this article, which charts the potential benefits of lenticule extraction for patients–and the shortcomings that providers must be aware of. While LASIK might not disappear anytime soon, it’s clear the laser refractive surgery landscape is very different now than just one year ago.

ESCRS 2023: Presbyopia treatment with microporation therapeutic technology by Ace Vision Group

Much of our most fascinating content this year came from in-depth conversations with industry leaders at conferences. AnnMarie Hipsley, DPT, PhD, Founder and CEO of Ace Vision Group, met with Ophthalmology Times Europe at the 2023 European Society of Cataract and Refractive Surgeons (ESCRS) meeting to discuss Ace Vision Group's microporation therapeutic technology, used to treat presbyopia. Novel treatments are quickly expanding the range of treatments available for patients with presbyopia, and Dr Hipsley indicated the condition will become a focal point for the eye care space in the days to come.

She used microporation therapeutic technology as an example of the accessible, effective treatments that are newly available to patients. “It's a true biomechanical treatment that's attacking this ocular rigidity from cross-linking in the sclera,” she explained. “It restores the natural dynamic range of focus function in the eye that moves the lens. It's so simple that it seems hard to wrap your brain around. But, it's been a really long journey to get here.”

To hear Dr Hipsley explain the research at length, watch the video here.

Restoring vision through retinal ganglion cell repopulation

Cell therapies are among the most fascinating–and complex–treatment modalities gaining popularity in eye care. In our May issue, Thomas V. Johnson III, MD, PhD, of Wilmer Eye Institute at Johns Hopkins Univeristy School of Medicine in Baltimore, Maryland, dove into the topic of retinal ganglion cell (RGC) repopulation.

Ophthalmology is pioneering the field with clinical trials of stem cell-derived retinal pigment epithelium and photoreceptor transplantation, which could potentially restore vision in diseases such as age-related macular degeneration and macular dystrophies. There are staggering implications to consider when researching potential treatments for optic neuropathies. Optic nerve diseases are both prevalent and irreversible; glaucoma alone affects more than 80 million individuals worldwide.

“The list of challenges in making functional RGC replacement a reality is daunting and will require therapeutic manipulation of cellular pathways involving neuronal survival, migration, dendritogenesis and axogenesis, pathfinding, synaptogenesis and myelination,” Dr Johnson wrote. But, there is reason to be hopeful. “Although the concept of optic nerve regeneration has long been the subject of fantasy, recent advances in neuroscience have converged to a point where functional RGC replacement may now be feasible,” he said.

Learn more about the promising breakthroughs in this space by reading the full article here.

SOE 2023: Optic neuropathy versus maculopathy

Advances in imaging technology have been one of the biggest instigators of broad-scale change in the field of ophthalmology. Physicians are now able to answer questions that have challenged ophthalmologists for years. During the European Society of Ophthalmology (SOE) Congress, held in Prague, Czech Republic, Nicholas Volpe, MD, spoke on one such benefit of optical coherence tomography (OCT).

In his presentation, “Optic Neuropathy Versus Maculopathy,” Dr Volpe addressed recent developments in this area. “This has for ages been a very hot topic for ophthalmologists, because there are a group of patients that have unexplained vision loss and relatively normal appearing fundi, that is both the macula and the optic nerve,” he said. “At first glance [they] appear to be healthy. And for decades, we would go back and forth–is this an optic nerve problem? Is it a macular problem?”

But the conversation has been “revolutionised” by the advent of OCT, he said, as the imaging technique has provided “a much finer anatomic view of what's happening in the retina.” Especially when combined with other forms of testing, Dr Volpe said, physicians have more certainty than ever about the best treatment protocol for their patients.

Dr Volpe spoke with David Hutton about his presentation – watch the video here.

Disease activity criteria shapes dosing interval outcomes in clinical trials

Marco Zarbin, MD, PhD, FACS, delivered his talk, “An Assessment of the Impact of Disease Activity Criteria on Dosing Interval Assignment in Clinical Trial Patients with Neovascular AMD,” at this year’s American Society of Retina Specialists (ASRS) meeting. Following the event in Seattle, Washington, we recapped the highlights of his presentation for the November print edition of Ophthalmology Times Europe. In a testament to the relevance of his chosen topic, this article, published in the last few weeks of 2023, quickly became one of our most-read stories of the year.

“The take-home message of this talk is that the definition of active disease in clinical trials affects the estimates of the durability of the agents that are tested in those trials,” Dr Zarbin explained early in his presentation. Referencing a set of clinical studies for neovascular age-related macular degeneration (nAMD), the CANDELA and PULSAR trials, Dr Zarbin noted that differences in active disease criteria were reflected in the study outcomes.

“It may not be surprising that the durability estimates were not the same,” Dr Zarbin said. “In CANDELA, where either a change in vision or a change in anatomy mandated an injection, about 53% of the patients could be maintained with injections every 12 weeks, whereas in the PULSAR trial, where both a change in vision and a change in anatomy were required to mandate an injection, durability increased such that 83% of the patients could be maintained with injections every 12 weeks or longer.”


See the full story here, with key takeaways that are vital for any practice.

A review of our most important content from throughout the year

Looking back, looking forward: top stories from Ophthalmology Times Europe 2023

Familial exudative vitreoretinopathy (FEVR) is an inherited retinal disease that disrupts normal blood vessel formation in the retina. Symptoms can range from mild visual deficits to severe visual impairment or even blindness. Accurate diagnosis of FEVR is challenging because its symptoms—such as retinal detachment and abnormal blood vessels—closely resemble those of other retinal diseases, including retinopathy of prematurity (ROP), Coats disease, and persistent fetal vasculature (PFV). Diagnosis often requires widefield angiography or genetic testing. Due to the overlap of symptoms with other conditions, especially in children, FEVR is frequently misdiagnosed, underscoring the critical role of genetic testing in guiding appropriate management.

Recent research highlighted the role of genetic testing in confirming FEVR diagnoses. The retrospective study reviewed cases from 104 paediatric patients referred with suspected FEVR.

 Genetic testing confirmed FEVR in 55 of these cases, revealing that 60% of patients with confirmed FEVR had initially received incorrect diagnoses. The average age at diagnosis was slightly higher in patients with revised diagnoses compared with those initially diagnosed with FEVR, suggesting diagnostic delays may impact disease progression.

Figures

The study identified several conditions commonly misdiagnosed as FEVR. Particularly in cases of late-preterm infants, ROP was the most frequent misdiagnosis, accounting for about 39% of cases.

 Besides genetic testing that can confirm the diagnosis, fluorescein angiography (FA) is valuable imaging technique for differentiating FEVR from ROP, as both conditions share similar clinical presentations, particularly peripheral retinal avascularity and abnormal vessel growth (

). In FEVR, the FA typically shows symmetric or many times asymmetric peripheral avascular retina without the distinct ridge formation and the organised vascular pattern seen in ROP. Also, there may be abrupt termination of blood vessels at the vascular-avascular junction with signs of neovascularisation or straightening of peripheral vessels, pinpoint areas of hyperfluorescence and segmental areas of vascular leakage.

PFV was misdiagnosed in 15% of cases, partly due to the similarities in retinal vascular anomalies between PFV and FEVR

. Key differences help distinguish PFV from FEVR, such as the presence of retinal folds that connect a stalk extending from the optic disc to the posterior lens in PFV—a distinctive structure not found in FEVR. FEVR is a posterior-temporal-anterior retinal fold vs PFV that is from the nerve to the lens. Additionally, PFV lacks a genetic pattern and may show distinct lens abnormalities, such as a thickened or elongated ciliary process and sometimes a shallow anterior chamber, which are not characteristic of FEVR. Recent observations suggest that unilateral PFV may be a bilateral, asymmetric condition, as retinal vascular abnormalities have been detected in most fellow eyes of patients with PFV. FA highlights further distinctions. In PFV, the affected eye may display leakage from persistent vessels, while the fellow eye can exhibit vascular abnormalities and in 67.1% peripheral vessel avascularity, a feature that, while present in both FEVR and PFV, differs in the specific vascular patterns observed.

 OCT adds diagnostic value by revealing a vascularised stalk in the affected eye in PFV and often a Bergmeister papilla in the fellow eye, imaging characteristics that are helpful for accurate differentiation.

Coats disease, which is misdiagnosed as FEVR in about 7% of cases, shares features with FEVR such as abnormal vascular development and retinal exudation.

 However, Coats disease typically affects only one eye, primarily in young boys, and does not follow a hereditary pattern, whereas FEVR often presents in both eyes. A distinguishing feature of Coats disease is the presence of “light bulb” aneurysms and significant leakage seen on fluorescein angiography, which are not usually observed in FEVR.

 On OCT, Coats disease often reveals extensive intraretinal and subretinal fluid, along with hyperreflective exudates caused by severe vessel leakage. Retinal cysts, outer retinal disruptions, retinal schisis formation and retinal thickening due to chronic exudation are also commonly seen in Coats disease.

The study emphasised the value of genetic testing as a diagnostic tool to confirm FEVR, especially in cases with atypical presentation. Genetic testing can identify pathogenic mutations in genes associated with FEVR, allowing clinicians to differentiate it from similar conditions. Key genes in FEVR, including 

, affect vascular development pathways. When mutations in these genes are present, a diagnosis of FEVR becomes more certain.

Genetic testing is recommended for patients with suspected FEVR when patients have ambiguous clinical presentation; when the family history suggests a hereditary condition, even in the absence of obvious symptoms in family members; and in cases in which initial treatments fail or symptoms persist. A confirmed diagnosis of FEVR aids in several aspects of patient management. It enables targeted treatments and family counseling by providing insights valuable for family planning and identifying relatives at potential risk, allowing for early detection and intervention. Additionally, patients with confirmed FEVR require long-term monitoring, even if symptoms are mild initially, as regular imaging and follow-up can detect any progression early on, supporting prompt treatment when necessary.

While genetic testing has clear benefits, there are limitations for its use. First, it can be expensive and may not be accessible, depending on patients' health care coverage. Moreover, not all FEVR cases have identifiable mutations in known genes. In this study, genetic mutations were only found in 53% of phenotypic FEVR cases,

 which is consistent with current literature.

Genetic testing not only prevents misdiagnosis but also helps clinicians tailor treatments, monitor disease progression, and provide valuable family counseling. Given the high rate of initial misdiagnoses, ophthalmologists should consider incorporating genetic testing into their diagnostic workflows for paediatric retinal disorders. This proactive approach can lead to better patient outcomes, especially for those with atypical presentations or a family history suggestive of hereditary eye disease.

1. Hudson JL, da Cruz NFS, Kunkler AL, Carletti P, Negron CI, Berrocal AM. Revision of Initial Referral Diagnosis after Genotypic Confirmation of Familial Exudative Vitreoretinopathy. 

2. John VJ, McClintic JI, Hess DJ, Berrocal AM. Retinopathy of Prematurity Versus Familial Exudative Vitreoretinopathy: Report on Clinical and Angiographic Findings. 

3. Laura DM, Staropoli PC, Patel NA, Yannuzzi NA, Nolan RP, Al-Khersan H, Fan KC, Flynn HW Jr, Acon D, Negron CI, Berrocal AM. Widefield Fluorescein Angiography in the Fellow Eyes of Patients with Presumed Unilateral Persistent Fetal Vasculature. 

4. da Cruz NFS, Sengillo JD, Hudson JL, Carletti P, de Oliveira G, Negron CI, Felder MB, Berrocal AM. Intraoperative OCT Angiography in Pediatric Patients with Persistent Fetal Vasculature. 

5. Jeng-Miller KW, Soomro T, Scott NL, et al. Longitudinal examination of fellow-eye vascular anomalies in Coats’ disease with widefield fluorescein angiography: a multicenter study. 

6. Ashkenazy N, Acon D, Kalavar M, Berrocal AM. Optical coherence tomography angiography and multimodal imaging in the management of coats’ disease. 

7. Scott NL, Cernichiaro-Espinosa LA, Russell JF, Murray TG, Dubovy SR, Berrocal AM. Retinoschisis in Coats Disease: Clinical Picture, Therapeutic Considerations, and Management Outcomes. 

. 2020;5(3):251-257. doi: 10.1177/2474126420954306

Natasha F. S. da Cruz, MD, PhD | E: natashafscruz@gmail.com

da Cruz is from Centro Ocular, Belém; Assistant of ROP at Santa Casa de Misericórdia do Pará; and completed a surgical retina fellowship and PhD at Federal University of São Paulo, all in Brazil. She completed a paediatric retina fellowship at Bascom Palmer Eye Institute, Miami, Florida.

Julia L. Hudson, MD | E: julia.hudson116@gmail.com

Hudson is from Associated Vitreoretinal and Uveitis Consultants in Carmel, Indiana.She studied at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, Pennsylvania, and completed her residency and surgical retina fellowship at Bascom Palmer Eye Institute, Miami, Florida.

Audina M. Berrocal, MD | E: ABerrocal@med.miami.edu

Berrocal is a professor of clinical ophthalmology, medical director of paediatric retina and retinopathy of prematurity, and vitreoretinal fellowship director at Bascom Palmer Eye Institute, in Miami, Florida.

A confirmed diagnosis of familial exudative vitreoretinopathy aids in several aspects of patient management

Putting diagnostic accuracy to the test

Hyperopic treatments have long been a topic of debate, with corneal-based options often pushed aside in favor of intraocular lenses (IOLs). However, recent advancements have reignited interest in corneal laser treatments, particularly with the evolution of LASIK and the introduction of Lenticule Extraction for hyperopia. Officially launched at the ESCRS Barcelona 2024, ZEISS SMILE pro for hyperopia is available as a new application on the ZEISS VISUMAX 800 femtosecond laser platform.

The implementation of SMILE pro for hyperopia on the VISUMAX 800, ZEISS Medical Technology’s most advanced laser system, marks a significant milestone in hyperopia treatment. This breakthrough in hyperopic treatment has shown outcomes comparable to hyperopic LASIK, while offering key benefits of ZEISS SMILE and SMILE pro such as minimized dry eye symptoms and reduced aberration induction.

Step-by-step to success - The journey of Lenticule Extraction for hyperopic patients

While ZEISS SMILE has been successfully used for myopia for years, hyperopic treatments faced initial setbacks, particularly with early prototypes like FLEx (Carl Zeiss Meditec AG), which lacked effective transition zones and used small optical zones. These early designs resulted in poor visual quality and unacceptable levels of regression, causing many to question whether Lenticule Extraction could ever be a viable option for hyperopia.

However, by redesigning the lenticule geometry to include an expanded transition zone and a larger optical zone, ZEISS SMILE pro has become an effective alternative to LASIK for hyperopia. The final lenticule geometry consisted of an optical zone of 6.3 mm with a transition zone of 2 mm, corresponding to a total lenticule diameter of 8.3 mm. A minimum lenticule thickness of 30 μm was used to ensure minimum interface interaction between the lenticule and cap cuts.

Feasibility studies conducted in Nepal using this updated lenticule profile found that the effective zone on topography was equivalent to that achieved by LASIK with a 7 mm optical zone using the ZEISS MEL 90 excimer laser.

 In the same study, it was also found that the centration achieved with hyperopia treatment with Lenticule Extraction (ZEISS SMILE) was no different to hyperopic LASIK, and the visual and refractive results were promising.

Following these studies, a prospective multicenter trial to investigate Lenticule Extraction with ZEISS SMILE for hyperopia was conducted across eight global sites from a diverse range of locations and was published in the Journal of Refractive Surgery in 2022.

 The study included 374 eyes with hyperopia up to +6.00 D and 12-month follow up using an updated nomogram based on the previous results. Overall, it was found that Lenticule Extraction for hyperopia achieved the same level of safety and efficacy as LASIK with the ZEISS MEL 90 excimer laser.

 In this study, the uncorrected distance visual acuity (UDVA) was within one line of their preoperative corrected distance visual acuity (CDVA) in 93% of patients. The refractive stability and visual outcomes were excellent, with no clinically significant loss of contrast sensitivity.

Here we describe the case of a 30-year-old male who presented for refractive surgical correction for hyperopia in both eyes. His refraction was +3.25 -1.75 x 78 (20/20) in the right eye and +3.75 -2.25 x 97 (20/20) in the left eye. He was a contact lens wearer and reported experiencing discomfort for the past eight years, for which he regularly used eye drops. The topography, tomography, and corneal thickness were all normal, and was therefore a suitable candidate for corneal laser refractive surgery. The mean keratometry was 43.89 D in the right eye and 43.91 D in the left eye, so there was ample scope for steepening. In this case, Lenticule Extraction for hyperopia was performed using the ZEISS VISUMAX 800. ZEISS SMILE pro was chosen due to the faster treatment time in addition to its minimally invasive nature and the minimization of dry eye symptoms, a key benefit for this patient.

Back to the cornea – Treating hyperopic patients with Lenticule Extraction

The treatment was planned using the standardized lenticule geometry as described above. Whereas the previous clinical trials had all been performed using the first-generation ZEISS VisuMax, the introduction of the ZEISS VISUMAX 800 includes improvements to the docking procedure including the centration assistant CentraLign

 cyclotorsion adjustment. The iris image is obtained using the ZEISS IOLMaster 700 and digitally imported into the treatment plan. During surgery, the CentraLign algorithm automatically detects the pupil and guides the surgeon to the intended treatment center. After applying suction, the system automatically calculates the cyclotorsion rotation required based on the live image of the iris.

We might expect a benefit in outcomes for cases with high astigmatism such as this patient. The other benefit of the ZEISS VISUMAX 800 is the faster cutting time, which reduces the risk of suction loss, particularly for hyperopic ZEISS SMILE pro where the overall cutting time is longer than for myopic treatments due to the larger lenticule. This aspect not only the potential of minimizing the risk of complications but also contributes to a smoother surgical experience. Due to the large optical zone required for a stable hyperopic correction, the M size contact glass is used with a cap diameter of 8.8 mm. The surgical technique is essentially the same as for myopic ZEISS SMILE or SMILE pro, except that a modified version of the Reinstein SMILE Separator should be used that has a longer 9-mm separating arm (compared to 8 mm for the similar myopic instrument).

This enables the safe separation of the interfaces across the larger cap diameter without the instrument stressing the small incision. Careful separation of the central thinnest region of the lenticule is advised. A course of mild corticosteroids for 1 month was given on completion of the standard first week post-SMILE/SMILE pro medications, in order to prevent interface haze formation.

At the day one appointment, the corneas were clear and the patient was comfortable. UDVA was 20/32 in both eyes with a spherical equivalent refraction of -0.50 D in the right eye and -0.75 D in the left eye. This slight myopic refraction would be expected to shift towards emmetropia with corneal healing and epithelial remodeling over the first 3-6 months, as observed in the previous study and after hyperopic LASIK.

 The topography showed a large and optical zone well centered on the corneal vertex (Figure 1).

The journey of hyperopic corneal treatments from near abandonment to a promising resurgence is a testament to the power of perseverance, research, and innovation in refractive surgery. This has been achieved through our understanding of optical zone and transition zone design to optimize refractive stability, centration relative to the corneal vertex rather than the entrance pupil center and the importance of epithelial mapping for evaluating risks associated with corneal steepening.

Lenticule Extraction for hyperopia with ZEISS SMILE pro presents several advantages over clear lens exchange that make it a compelling option for both surgeons and patients. With its ability to provide outcomes comparable to hyperopic LASIK with less tear film depression, ZEISS SMILE pro for hyperopia using the ZEISS VISUMAX 800 represents a promising advancement in refractive surgery, aligning with the goal of delivering high-quality care and improved patient satisfaction.

 is Medical Director of London Vision Clinic. He is also consultant to and receives travel expenses from Carl Zeiss Meditec AG, and has financial interest in ArcScan Inc.

 Reinstein DZ, Archer TJ, Gobbe M, Bartoli E. Corneal sensitivity after small-incision lenticule extraction and laser in situ keratomileusis. J C ataract Refract Surg. 2015 Aug;41(8):1580-7.

 Reinstein DZ, Pradhan KR, Carp GI, Archer TJ, Gobbe M, Sekundo W, Khan R, Citron K, Dhungana P. Small Incision Lenticule Extraction (SMILE) for Hyperopia: Optical Zone Centration. J Refract Surg. 2017 Mar 1;33(3):150-156

 Pradhan KR, Reinstein DZ, Carp GI, Archer TJ, Dhungana P. Small Incision Lenticule Extraction (SMILE) for Hyperopia: 12-Month Refractive and Visual Outcomes. J Refract Surg. 2019 Jul 1;35(7):442-450. doi: 10.3928/1081597X-20190529-01. PMID: 31298724.

 Reinstein DZ, Sekundo W, Archer TJ, Stodulka P, Ganesh S, Cochener B, Blum M, Wang Y, Zhou X. SMILE for Hyperopia With and Without Astigmatism: Results of a Prospective Multicenter 12-Month Study. J Refract Surg. 2022 Dec;38(12):760-769.

 Reinstein DZ, Carp GI, Archer TJ, Day AC, Vida RS. Outcomes for Hyperopic LASIK With the MEL 90® Excimer Laser. J Refract Surg. 2018 Dec 1;34(12):799-808.

 Reinstein DZ, Gobbe M, Archer TJ. Coaxially sighted corneal light reflex versus entrance pupil center centration of moderate to high hyperopic corneal ablations in eyes with small and large angle kappa. J Refract Surg. 2013 Aug;29(8):518-25.

 Reinstein DZ, Carp GI, Archer TJ, Buick T, Gobbe M, Rowe EL, Jukic M, Brandon E, Moore J, Moore T. LASIK for the Correction of High Hyperopic Astigmatism With Epithelial Thickness Monitoring. J Refract Surg. 2017 May 1;33(5):314-321.

Industry updates from Floretina ICOOR 2024

This article is dedicated to the memory of Ramin Tadayoni, MD, PhD.

Data from the Global Burden of Disease Study showed that in 2020, diabetic retinopathy (DR) ranked as the fifth most common cause of blindness and moderate and severe vision impairment among adults aged 50 years and older.

 Despite advances in medical/pharmacologic therapy for achieving systemic metabolic control and for managing diabetic eye disease, the burden of these consequences of DR may be expected to increase in association with population aging and as the prevalence of diabetes continues to rise.

Surgical intervention with vitrectomy is required for the management of some vision-threatening complications of proliferative DR, including tractional retinal detachment involving or threatening the fovea, persistent vitreous hemorrhage, mixed retinal detachment, and tractional diabetic macular edema. The surgical goals include relieving traction, removing fibrovascular proliferation and the posterior hyaloid, and ensuring retinal attachment with tamponade as needed. Determining the need and urgency for performing vitrectomy and achieving optimal functional and anatomical surgical outcomes depends on the ability to visualize the pathology. Developments in technologies for diagnostic imaging and surgical visualization enable clinicians to make informed decisions by visualizing pathology, and subsequently improving patient outcomes.

In addition to establishing the indication for surgery, findings on preoperative imaging are used for planning the procedure and have prognostic significance. Referral to preoperative images facilitates location of interventional targets, and there is accumulating evidence demonstrating that certain features in eyes with DR are predictors for risk of DR progression and visual outcome.

Color fundus photography (CFP) has been the mainstay for evaluating eyes with DR. However, the 7-standard ETDRS fields provide a limited field of view (75°) and fail to capture pathology existing in the peripheral retina, which has become of significant importance for predicting progression of DR.3 In addition, visualization of the fibrovascular proliferation and its extension beyond the mid-periphery is critical for planning surgery in eyes with tractional retinal detachment (Figure 1). Currently available dedicated widefield and ultra-widefield camera systems provide single capture FOVs beyond the 7-field ETDRS area offering acquisition efficiency, enhanced patient comfort, and view beyond the mid-periphery. The ZEISS CLARUS is one such UWF fundus camera with a FOV of 133° for a single image and up to 267° with ultra-wide field montage.

In addition to CFP, optical coherence tomography (OCT) is a cornerstone in the evaluation and management of diabetic eye disease. OCT provides high resolution images of retinal morphology and relevant DR lesions that makes it a valuable aid in establishing the need for medical or surgical intervention and procedure planning. The detailed OCT images can also allow detection of pathology that can be overlooked on the color fundus photographs, such as small retinal breaks or areas of fibrovascular proliferation. OCT biomarkers such as Disorganization of the Retinal Inner Layers (DRIL) are also important for determining visual prognosis and treatment response of patients with diabetic macular edema (DME).

When used together, quality images from CFP and OCT enable understanding of the extent of proliferation and the connection of the posterior hyaloid to new vessels. Surgically this is important to understand where to initiate opening in the posterior hyaloid face.

Used to assess retinal vasculature, fluorescein angiography (FA) has also been a key diagnostic tool for imaging eyes with DR, and its utility has expanded with the development of widefield and ultra-widefield technologies. Nevertheless, FA is an invasive technique that carries risks and is contraindicated in certain patients. Furthermore, FA has limited depth resolution, and obtaining good quality images depends on operator expertise.

OCT angiography (OCTA) is a noninvasive study that provides depth-resolved images of the retinal microvasculature without need for a highly trained operator. However, OCTA does not identify leakage, and so it serves as a complement to FA rather than an alternative. OCTA is especially important for visualizing changes to the foveal avascular zone (FAZ), retinal ischemia, and changes to the vascular density that are difficult to detect and quantify on FA (Figure 1). These OCTA biomarkers provide diagnostic, prognostic, and predictive information related to visual outcome, risk of progression, and response to treatment (intravitreal steroid or anti-VEGF).

Advances in intra-operative visualization

Obtaining maximal visualization intraoperatively is critical to the success of vitrectomy performed for complications of proliferative diabetic retinopathy (PDR). The utilization of a microscope-integrated intraoperative OCT (iOCT) is very crucial as it addresses this need by enhancing identification of existing pathology and allowing surgeons to operate with greater safety and precision near the retina.

Use of a heads-up three-dimensional (3D) digital viewing system, such as the ZEISS ARTEVO 800 or its successor, the ZEISS ARTEVO 850, also provides benefits when performing vitrectomy for complications of DR. The 3D digital visualization offers enhanced resolution, magnification, and depth of field, with the latter having particular value in cases where the fibrovascular proliferation is attached to the posterior pole. This technology also allows the operation to be performed with a lower light intensity that results in less glare for the surgeon and less risk of phototoxicity for the patient. Moreover, surgeons benefit from the ergonomic advantages of using a heads-up display.

The following cases involving patients with PDR illustrate how I use advanced imaging technologies to help me with diagnosis, surgical planning, and intraoperative decision-making.

A 29-year-old patient presented with significant vision loss in the left eye. On examination she was found to have 20/200 BCVA associated with tractional retinal detachment. The B scan OCT image showed vast fibrovascular proliferation along the arcade and traction on the macula. The patient was scheduled for surgery (Figure 2).

Andrzej Grzybowski, MD, PhD, MBA, MAE

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