Ophthalmic innovation by the decades: The 2010s

From the 2010s to the present, the existing technologies in the clinic and operating room have been improved with the goals of providing patients with earlier and more precise diagnostics and streamlined management. Here are the top technologic picks from the most recent past and the direction Ophthalmology is headed in the near future.

Artificial intelligence

During the previous decade, the development and use of artificial intelligence (AI) have expanded by leaps and bounds in the technology’s abilities to detect and manage ocular diseases, such as diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (AMD).

The use of AI will revolutionize ophthalmic care through automated screening, precision diagnostics, and optimized treatment planning.^1,2

“In DR, AI algorithms analyze retinal images to accurately identify lesions, which helps clinicians in ophthalmology practice. Systems like IDx-DR (IDx Technologies Inc.) are FDA-approved for autonomous detection of referable DR. For glaucoma, deep-learning models assess optic nerve head morphology in fundus photographs to detect damage. In AMD, AI can quantify drusen and diagnose disease severity from both color fundus and optical coherence tomography (OCT) images. AI also has been used in screening for retinopathy of prematurity, keratoconus, and dry eye disease,”¹ according to a recent review.

AI also can help clinicians manage diseases by predicting their progression and the response to anti-vascular endothelial growth factor (VEGF) therapies. These capabilities are still works in progress because of limitations such as the quality and diversity of training data, lack of rigorous clinical validation, and challenges in regulatory approval and clinician trust.¹ Other current barriers are the integration of AI into existing clinical workflows and ensuring transparency in AI decision-making processes.^1,2

However, as mentioned, improving the translation of AI research into viable clinical tools continues.¹ Algorithm performance depends heavily on the quality and diversity of the training data. “Black box” AI systems that lack interpretability raise justified skepticism, and their seamless integration into existing clinical practice is yet to be achieved.¹

Investigators remain focused on the future, however, because they believe that “AI holds immense potential to provide clinicians with data-driven, objective assessments that could radically transform ophthalmic care.³

Gene therapy

The focus of ocular gene therapy in the very recent past has been on diseases linked to various genetic factors. “The eye is an ideal candidate for gene therapy due to its unique characteristics, such as easy accessibility and the ability to target both corneal and retinal conditions, including retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), AMD, and Stargardt disease. Currently, the literature documents 33 clinical trials in this field, with the most promising results emerging from trials focused on LCA,” according to Maurya et al.⁴

The initial research prompted further forays into glaucoma, AMD, RP, and choroideremia. Those authors explained that the effectiveness of gene therapy requires efficient, sustained delivery of genetic material to specific cells. Investigators have used viral vectors to that end, although there are risks of immune reactions and genetic mutations have led to the development of non-viral vector systems.⁴

The first gene therapy approved by the FDA in 2017 was Luxturna (voretigene neparvovec-rzyl, Spark Therapeutics) developed to treat an inherited retinal disease, LCA. According to the American Academy of Ophthalmology,⁵ this therapy uses an AAV2 viral vector to replace mutated copies of the RPE65 gene that cause several types of autosomal recessive retinal dystrophies, including subtypes of RP and LCA. The phase 3 study, published in The Lancet showed that “a one-time subretinal injection of Luxturna induced substantial gains in the light perception ability of both pediatric and adult patients with biallelic RPE65 mutations. The improvements were stable for up to 3 years and longer.⁶ This advance was seen as a paradigm shift for patients with inherited retinal disease.⁵

Gene editing

Emerging techniques like clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) and optogenetics, may be able to achieve visual restoration restore vision by modifying the genetic code.

CRISPR was first used in ophthalmology in a clinical trial to treat LCA type 10 in March 2020. A patient received an injection of the CRISPR-based therapy EDIT-101 into the eye at the Oregon Health & Science University's Casey Eye Institute in Portland. The procedure was performed to repair mutation in the CEP290 gene.⁷

Harvard Medical School researchers at Mass Eye and Ear in Boston conducted a proof-of-concept gene editing phase 1-2 study (Brilliance ClinicalTrials.gov number, NCT03872479) that evaluated the technology’s effects in patients with CEP290-associated inherited retinal degeneration.⁸

Fourteen patients received a subretinal injection of EDIT-101 in their worse eye. EDIT-101, the authors described, is a CRISPR/Cas9 gene-editing complex. The primary study outcome was safety.⁸

The authors reported, “Eleven participants (79%) had improvement in at least one of four key efficacy outcomes, whereas 6 (43%) had improvement in two or more outcomes. Four participants had a clinically meaningful improvement in the best-corrected visual acuity. Nearly half the participants (6 of 14) had a visually meaningful improvement in cone photoreceptor function as assessed with the use of full-field stimulus testing, of whom all but one had an improvement in at least one other outcome.”

The improvements in vision began at 3 months and were sustained during follow-up visits; one patient had sustained improvement up to year 2. “These findings support the presence of productive in vivo gene editing by EDIT-101, therapeutic levels of CEP290 protein expression, and enhanced cone photoreceptor function,”⁸ the authors commented. The findings supported continued research and clinical trials of CRISPR therapies for inherited retinal disorders.

Optogenetics

Recent optogenetics advances hold promise for vision restoration in degenerative eye diseases. Optogenetics is defined as techniques that use light to control the cellular activity of targeted cells. Although optogenetics is a relatively new technology, multiple therapeutic options are already being explored in pre-clinical and phase I/II clinical trials with the aim of developing novel, safe, and effective treatments for major blinding eye diseases, such as glaucoma and RP. Optogenetic approaches to visual restoration are primarily aimed at replacing lost or dysfunctional photoreceptors by inserting light-sensitive proteins into downstream retinal neurons that have no intrinsic light sensitivity. Such approaches are attractive because they are agnostic to the genetic causes of retinal degeneration, which raises hopes that all forms of retinal dystrophic and degenerative diseases could become treatable.⁹

Nature Methods described optogenetics as the “Method of the Year” in 2010 in science and engineering.¹⁰ Science reported optogenetics as one of the “Breakthroughs of the Decade.”¹¹ In 2021, the technology saw its first medical use when a patient who was blind as a result of RP regained partial vision.¹² An adeno-associated viral vector encoding ChrimsonR was injected into the eye of this 58-year-old patient who had had RP for 40 years. Combined with light stimulation via engineered goggles to activate optogenetically transduced retinal ganglion cells, the patient reported perceiving, locating, counting, and touching different objects using the vector-treated eye alone while wearing the goggles.¹²

A promising optogenetics therapy is MCO-010 (Nanoscope Therapeutics), which is currently being studied as a treatment for both RP and Stargardt disease, according to Modi et al.¹¹ MCO-010 has received both fast track and orphan drug designations from the FDA for these conditions. The molecule is delivered by an adeno-associated virus introduced to the eye in a single intravitreal injection.¹³

In addition to MCO-010, other optogenetic therapies for RP include GS030 (GenSight Biologics); RST-001 (RetroSense/Allergan); BS01 (Bionic Sight), and RTx-015 (Ray Therapeutics). These therapies differ with respect to their cellular targets, kinetics, and spectral and light sensitivity.¹⁴

Novel approach to study DNA damage

Emily C. Beckwitt, PhD, a postdoctoral associate at The Rockefeller University, New York, and her team are taking a deep dive into determining the whys and hows of DNA damage at the molecular level. This line of study is investigating how yeast senses DNA damage in the cell cycle checkpoint, ie, the ataxia telangiectasia and Rad3-related pathway, in humans.

Beckwitt explained that when excessive damage accumulates in cells, the cells must prioritize repair before they can continue to divide. If the cells divide with excessive DNA damage, that leads to cancer-causing mutations.

“Humans have evolved to have something called ‘the replication stress and DNA damage checkpoint,’ which is a very complicated pathway that basically senses if there is too much damage and tells the cell to stop everything until repair takes place. It is a fundamental/intrinsic part of normal cell functioning because DNA damage is unavoidable. As in regular cellular metabolism and sun exposure, for example, our DNA is constantlybeing damaged and repaired. The checkpoint is like a built-in fail safe for the cell if things get out of control,” she explained.

All eukaryotes, ie, organisms that have cells in which the DNA is housed in a nucleus, have this pathway. Dr. Beckwitt is working with yeast proteins, which is very similar to what goes on in humans. The goal is to determine how these proteins recognize DNA damage and become activated in the very early steps of the pathway. Down the line, the hope is that this research will inform some clinical work, she said.

The medical connections of this topic have been studied by other groups, she pointed out. The first involves defective DNA damage checkpoint proteins that cannot sense damage; in this case the cells continue dividing and propagating damage, making the organism more vulnerable to mutation/cancer. A second involves normal checkpoint proteins, but cancer has developed for another reason; in this event one approach would be toinhibit the checkpoint with drugs to kill the cancer cells by making them even more out of control.

Advances in OCT

OCT became in invaluable component of intraocular surgery in the late 2000s, when surgeons recognized the potential to visualize real-time tissue and surgical interfaces.1 Intraoperative OCT transformed how retina specialists visualize and address retinal conditions. Its intraoperative adaptation allows for real-time feedback during surgery, enabling precise assessment of microstructural changes and verification of surgical outcomes.¹⁵

Since it introduced in 1991, the major advancements in OCT have included the development of spectral-domain OCT, swept-source OCT (SS-OCT) to achieve wider fields and faster scans, OCT angiography for non-invasive 3D blood flow imaging, intraoperative OCT for real-time surgical guidance, and the expansion of technology into home monitoring devices and handheld versions. These innovations have led to improved detection of retinal and choroidal diseases, improved surgical outcomes, and new diagnostic possibilities,¹⁵ according to Eric Lai, MD, and colleagues.

The technology has advanced rapidly over the years.

• In 2010, Fourier-domain mode-locking (FDML) OCT was introduced, using FDML lasers for tissue scanning, providing very high speed and image clarity.
• In 2015, SD-OCT was combined with SS-OCT to improve image accuracy and depth.
• In 2020, advanced OCT angiography and molecular OCT were introduced, enabling imaging of blood flow and specific molecules.
• In 2024, OCT was applied to neurosurgery, occupational therapy and dermatology.¹⁶

Ali Mokhtari, MD, and colleagues predictedsignificant advancements on the horizon for OCT research and development across several key areas. “Enhancing resolution and imaging depth has become a primary focus, with scientists working to develop superior light sources and scanning techniques to improve image quality and enable deeper tissue penetration. Additionally, high-speed imaging is an important area of exploration, aiming to enhance imaging hardware and software while reducing motion artifacts, thereby facilitating real-time imaging capabilities,”¹⁶ they said.

They also noted thegrowing interest in ophthalmology in using OCT with other imaging modalities, such as fluorescence and ultrasound and in developing more accurate and reliable methods for early disease detection and evaluating therapeutic effectiveness.

A significant trend in OCT molecular imaging, the researchers pointed out, is the integration of AI and machine learning, particularly in predictive analytics. As AI networks are developed for segmentation, classification, and quantification, the need for manual analysis will lessen. Predictive models are also being created to estimate disease progression and therapeutic outcomes based on available OCT data, thereby assisting in treatment planning.

They also envision a future for interdisciplinary collaboration as OCT advances. “This involves integrating the expertise of physicists, engineers, clinicians, and computer scientists to enhance the translation of technological advancements into clinical practice. Such collaboration should also encompass legal and ethical considerations to protect emerging OCT technologies from misuse and to ensure respect for privacy and ethical standards in AI applications,” they explained.

Finally, simplifying OCT and developing cost-effective OCT systems is important for use in resource-limited settings, with a particular focus on miniaturization and cost reduction. “Furthermore, OCT is increasingly being applied in personalized medicine, in which imaging data are utilized to determine the most suitable treatment for individual patients. Algorithms analyze relevant information from databases to provide personalized treatment recommendations, thereby enhancing patient care,”¹⁶ they stated.

Treatments and pharmaceuticals

The first intravitreal anti-VEGF drugs developed in the early 2000s to treat wet AMD were bevacizumab (Avastin, Genentech Inc.), ranibizumab (Lucentis, Genentech Inc.). Aflibercept (Eylea, Regeneron Pharmaceuticals) followed in 2011, and then brolucizumab (Beovu, Novartis Pharmaceuticals) in 2019, faricimab (Vabysmo, Genentech) in 2022, and the high-dose aflibercept 8-mg formulation in 2023.

Other developments during this time were the introduction of biosimilars and drug delivery systems such as ocular implants, such as Susvimo (ranibizumab injection, Genentech). These innovations aim to improve efficacy and extend the time between injections.

A new drug to treat geographic atrophy, Izervay (avacincaptad pegol, Astellas Pharma, Inc.) was approved in 2023. While the drug does not stop progression of the end stage of AMD, it slows it.

Looking to the future, new treatment strategies in development aim to reduce the treatment burden for patients with wet AMD.¹⁷

In addition, gene therapies could offer hope for long-term control of wet AMD with one-time treatments. The pipeline of dry AMD treatments is expanding to include new drug candidates for geographic atrophy and Stargardt disease.¹⁷

Surgical innovation

The FDA approved the RxSight Inc. Light Adjustable Lens and Light Delivery Device, the first medical device system that can make small adjustments to the artificial lens’ power after cataract surgery so that the patient will have better vision when not using glasses.¹⁸

The RxSight intraocular lens is comprised of a material that reacts to ultraviolet light, which is delivered by the Light Delivery Device, 17-21 days postoperatively. Patients undergo three or four light treatments over a period of 1 to 2 weeks, each lasting 40 to 150 seconds, depending on the degree of the adjustment, according to the FDA press release.¹⁸

References

1. Hashemian H, Peto, T, Ambrosio Jr. R, et al. Application of artificial intelligence in ophthalmology: an updated comprehensive review. J Ophthalmic Vis Res. 2024;19:354–367. doi: 10.18502/jovr.v19i3.15893

2. Li Z, Wang L, Wu X, et al. Artificial intelligence in ophthalmology: The path to the real-world clinic. Cell Rep Med. 2023;4:101095. doi:10.1016/j.xcrm.2023.101095

3. Liu X, Faes L, Kale AU, et al. A comparison of deep learning performance against health-care professionals in detecting diseases from medical imaging: A systematic review and meta-analysis. Lancet Digit Health. 2019;1:e271–97. doi: 10.1016/S2589-7500(19)30123-2.

4. Maurya R, Vikal A, Narang RK, Patel P, Kurmi BD. Recent advancements and applications of ophthalmic gene therapy strategies: a breakthrough in ocular therapeutics. Exp Eye Res. 2024;245:109983. https://doi.org/10.1016/j.exer.2024.109983

5. Kovner A. FDA announces landmark approval of gene therapy for inherited retinal dystrophies. American Academy of Ophthalmology. 2017; December 19. https://www.aao.org/education/headline/fda-announces-landmark-approval-of-gene-therapy-in

6. Russell S, Bennett J, Wellman JA, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017;390:849–860.

7. White F. OHSU performs first-ever CRISPR gene editing within human body. OSHU News. 2020; published March 4. https://news.ohsu.edu/2020/03/04/ohsu-performs-first-ever-crispr-gene-editing-within-human-body#:~:text=BRILLIANCE%20trial-,Andreas%20Lauer%2C%20M.D.%2C%20right%2C%20performs%20the%20first%2Dever,for%20the%20BRILLIANCE%20clinical%20trial.

8. Pierce EA, Aleman TS, Jayasundera KT, et al. Gene editing for CEP290-associated retinal degeneration. N Engl J Med. 2024;390:1972-1984. DOI: 10.1056/NEJMoa2309915

9. Prosseda PP, Tran M, Kowal T, Wang B, Sun Y. Advances in ophthalmic optogenetics: approaches and applications.Biomolecules. 2022;12:269. doi: 10.3390/biom12020269

10. Editorial. Method of the Year 2010. Nat Methods. 2011;8:1. https://www.nature.com/articles/nmeth.f.321

11. News S. Insights of the decade. Stepping away from the trees for a look at the forest. Introduction. Science. 2010;330:1612–3.

12. Sahel JA, Boulanger-Scemama E, Pagot C, et al. Partial recovery of visual function in a blind patient after optogenetic therapy. Nat Med. 2021;27:1223–1229. https://doi.org/10.1038/s41591-021-01351-4

13. Modi Y, Ho AC, Bhattacharya S. Clinical trial download: the potential of optogenetic therapy. Retin Physician. 2024;21:18-20. https://www.retinalphysician.com/issues/2024/october/the-potential-of-optogenetic-therapy/

14. Ho AC. Optogenetics for retinal disease. Modern Retina. 2025; May/June. https://www.modernretina.com/view/optogenetics-for-retinal-disease#:~:text=The%20field%20of%20optogenetics%20is,light%20sensitivity%20(Table%201).

15. Lai EW, Lee TS, Schechet A. Clinical advances of intraoperative OCT in Vitreoretinal Surgery. Retin Physician. 2025;22:15-17.

16. Mokhtari A, Maris BM, Fiorini P. Survey on optical coherence tomography—technology and application. Bioengineering. 2025;12:65; https://doi.org/10.3390/bioengineering12010065

17. Weintraub A. Emerging treatments off new hope for dry and wet age-related macular degeneration. Macular Degeneration Research. 2025; https://www.brightfocus.org/resource/emerging-treatments-offer-new-hope-for-dry-and-wet-age-related-macular-degeneration/#:~:text=To%20reduce%20the%20need%20for%20frequent%20injections%2C%20some%20drug%20developers,will%20be%20completed%20next%20year.

18. FDA News Release. FDA approves first implanted lens that can be adjusted after cataract surgery to improve vision without eyeglasses in some patients. 2017; November 22. https://www.fda.gov/news-events/press-announcements/fda-approves-first-implanted-lens-can-be-adjusted-after-cataract-surgery-improve-vision-without#:~:text=FDA%20News%20Release-,FDA%20approves%20first%20implanted%20lens%20that%20can%20be%20adjusted%20after,vision%20when%20not%20using%20glasses.