The expectations of my patients have changed in recent years, with more now asking for independence from spectacles at all distances. However, I was not satisfied with the outcomes offered by multifocal, trifocal or traditional IOLs (with or without capsular tension rings).

Now, with the introduction of the next-generation RayOne EMV monofocal IOL (Rayner), I am able to offer many patients excellent vision at both intermediate and far distance, which satisfies much of their daily needs. The new IOL received a CE mark in June 2020.

The lens is designed to provide superior intermediate vision compared with standard monofocal IOLs and is the first and only IOL designed to enhance patient outcomes in a monovision setting; it can provide, on average, up to 2.25 D depth of focus when used with a 1.0 D offset. It is non-diffractive and dysphotopsia-free, with no zonal demarcation on the surface, and is designed to induce positive spherical aberration across a controlled aspheric surface.

There are no specific indications based on an individual’s profession, and patient selection typically depends on surgeon preference. In practice, surgeons prefer—and it is recommended that—the closest negative to zero is targeted for the dominant eye with approximately 0.75–1.0 D offset in the non-dominant eye. With the extended depth of vision provided by this lens, the dominant eye is more forgiving of post-operative myopic shift than with aberration-free aspheric IOLs.

Figure 1. Simple OVD injection into IOL cartridge.

In a first-in-eye series, patients who were implanted with this lens and followed for 1 month after surgery reported a high degree of satisfaction with refractive outcomes; 70% reported spectacle independence at distance, intermediate and near vision. No halo, glare, starbursts or haze were observed.

In addition, all patients were dysphotopsia free, and none reported trouble negotiating steps, stairs or kerbs due to changes in depth perception. Overall, no depth perception or contrast sensitivity issues were reported.

Surgeons participating in the study also responded with a great degree of satisfaction. They uniformly reported smooth lens transition with the preloaded injector (Figure 1), fine IOL control during insertion (Figure 2) and excellent stability and centration of the IOL in the capsular bag. All the participating surgeons reported reaching their targeted subjective refractive outcome.

Figure 2. Handy IOL implantation through the preloaded injector. 

No intraoperative or postoperative adverse effects were reported. One practice participating in the series administered a spectacle independence and visual functioning questionnaire to patients receiving the lens. All respondents reported no difficulty in reading medicine bottles, participating in sports, watching television or driving during the day or night.

The lens is compatible with a smartphone app that is associated with it and free-of-charge to Rayner customers. The app is a unique telehealth solution for collecting patient-reported outcomes data for the first 3 years after cataract surgery.

It is hoped that with this unique data-collection tool, we will be able to better evaluate clinical outcomes over time. Additional clinical studies are also planned to further contribute to the weight of evidence with this innovative technology.

Functional intermediate vision means that patients can read their mobile phone, use a computer, shop and enjoy a meal without the use of glasses. With the appropriate light, they can also read at near distance with the binocular use of both eyes, which is an important feature of this monofocal option.

I think that this lens will be an attractive option as many patients are asking for presbyopia correction and the previously available multifocal IOLs have not been able to achieve excellent vision results. This is sometimes because preoperative patient consultations have not fully identified the patient’s expected outcomes, especially with respect to the need for a period of postoperative adaptation with most multifocal IOLs.

For this reason, the new lens may be attractive for many clinics in Italy, as it will likely meet many patients’ expectations in terms of glasses independence and does not involve a period of adaptation after surgery. We have based the cost to patients on the price of the IOL and do not impose a premium charge for the implantation procedure itself.

I also explain to the patients of mine who are good candidates and considering the new lens that without the features that this particular lens provides, they will continue to replace glasses every few years for the rest of their lives, which of course will add up to considerable costs over time.

Although my clinic is still in its initial phase of experience with this lens, my patients and I have been very happy with the outcomes we have seen, including greater spectacle independence with few reports of visual disturbances. Additional data from the patient-reported outcomes database and further clinical studies will allow us to increase our degree of confidence in this new option in the monofocal setting.

With the ability to provide quality of vision for sports, socialising, computer use and other daily activities, the outcomes already seen in initial experience will likely translate to a better quality of life as well.

Dr Buratto is the director of the Centro Ambrosiano Oftalmico - Camo S.p.A. (Ophthalmic Microsurgery Centre) in Milan, Italy. He has no relevant financial disclosures.

Articles

Patients desire spectacle independence at all distances. Early experience with a recently launched IOL suggests that it can satisfy their demands for extended depth of vision.

New IOL offers patients greater spectacle independence over wider range

The American Academy of Ophthalmology (AAO) annual meeting was held November 12 to 15 at the Ernest N. Morial Convention Centre in New Orleans, Louisiana. The event included Subspecialty Days and a virtual component for remote participation.

Study reports that optic nerve pallor is prevalent in ZIKA virus patients

Dr Denise Freitas reported that the ocular findings in infants with congenital Zika virus syndrome were similar among the affected infants and occurred frequently. The most prevalent of the findings was optic nerve pallor.

Presbyopia-correcting drops provide hope for frustrated patients

Dr Cathleen McCabe describes how VUITY, the first and only FDA-approved eye drop to treat age-related blurry near vision, provides opportunities for patients looking for spectacle independence.

Mitomycin C associated with increase in corneal haze after corneal crosslinking

Dr Shady Awwad pointed out that the application of mitomycin C after corneal crosslinking does not prevent development of corneal haze after the procedure and instead contributes to development of more corneal haze.

Study of bimatoprost implant reports IOP reduction for 2 years or more

Dr Felipe Medeiros noted that a phase 3 clinical extension study of the bimatoprost implant found that patients’ IOP was lowered and stayed low with no additional treatment or changes in their visual fields.

Though rare, ocular surface tumours often prove deadly

Nathan Hall pointed out that an epidemiologic analysis of malignant ocular surface tumours found significant differences in geographic prevalence rates in the United States.

Study proves intra-arterial tissue plasminogen activator beneficial for treatment of central retinal artery occlusion

Intra-arterial tPA treatment could provide benefits for patients with central retinal artery occlusion.

Universal face masking reduces endophthalmitis incidence during anti-VEGF injections

Dr Sunir J. Garg speaks on the influence of COVID-19 universal face masking on the risk of endophthalmitis following intravitreal anti-VEGF injections.

Dosing variability with pre-filled syringes of aflibercept presents risk of overdose

Dr Roger A. Goldberg noted that small misalignments in the plunger can lead to possible overdosing.

Plasma metabolomic profiles could predict AMD progression

Dr Ines Lains explained that the mechanisms of AMD progression currently remain poorly understood and the tools to predict and halt progression are limited.

Drug delivery to retina via port delivery system is efficient for patients with wet AMD

In a poster presented at the American Academy of Ophthalmology 2021 annual meeting in New Orleans, Dr Mark Wieland noted that the port delivery system with ranibizumab provides drug delivery over an extended period.

Central subfield thickness changes linked to worse visual outcomes in DMO

Dr Ajay Kuriyan discusses his poster at AAO, "Fluctuations in central subfield thickness associated with worse visual outcomes in patients with diabetic macular oedema in clinical trial setting."

DMO treatment: Brolucizumab proves noninferior to aflibercept, requires fewer injections

Dr Dilsher Dhoot reported the results of the KESTREL and KITE in which brolucizumab was compared with aflibercept for treating diabetic macular oedema.

DMO: Study finds faricimab provides sustained retinal stability

Dr Veeral Sheth presented research that found faricimab, a bispecific monoclonal antibody, provided sustained retinal stability in patients with diabetic macular oedema (DMO) compared with other retinal treatments.

President John Saharek on the ImprimisRx pipeline, details 3 products

ImprimisRx President John Saharek shares an update on a few of the company's latest products during AAO 2021.

A brief overview of the plethora of findings presented at the 2021 American Academy of Ophthalmology meeting held November 12-15 in New Orleans, LA.

Review of findings presented at the American Academy of Ophthalmology annual meeting

The port delivery system with ranibizumab (Susvimo, Roche/Genentech), an ocular implant approved recently to treat wet age-related macular degeneration, provides drug delivery over an extended period. The implant provides a dose of 100 mg/ml that is released over 6 months. The implant was approved based on the results of the Archway phase 3 study in which the results of the implant were compared with the results achieved with injections of ranibizumab alone.

Retina specialists Drs Mark Wieland and Jay Stewart looked at the implant’s release and refill-exchange efficiency in vitro and reported that “about 70% of the ranibizumab 100 mg/mL was released from the implant over 6 months; levels were unmeasurable after 450 days.”

Dr Weiland discussed their findings during a presentation at the American Academy of Ophthalmology 2021 annual meeting in New Orleans.

Specifically, the mean respective active release rates at 6 months, expressed as µg/day, were 3.95, 3.99, 3.85, and 4.00 at the initial filling of the implant and at the first, second, and third refill/exchanges, they reported.

They also found that during refilling of the implant, about 98% of the previous implant contents were replaced with fresh drug in one 100 mg/mL refill.

The investigators concluded that the PDS continuously and reproducibly delivers ranibizumab over a period of months while maintaining its potency.

's Sheryl Stevenson speaks with Dr Sunir J. Garg, co-director of retina research at the Wills Eye Hospital in Baltimore, Maryland, United States, on the highlights of his presentation at the 2021 annual American Academy of Ophthalmology (AAO) meeting regarding the impact of COVID-19 universal face masking on the risk of endophthalmitis following intravitreal anti-vascular endothelial growth factor (VEGF) injections.

The American Academy of Ophthalmology (AAO) annual meeting was held November 12 to 15 at the Ernest N. Morial Convention Centre in New Orleans, Louisiana, United States. The event included Subspecialty Days and a virtual component for remote participation.

Videos

In a study, outlined at the American Academy of Ophthalmology 2021 annual meeting in New Orleans, Dr Veeral Sheth and colleagues reported that faricimab, a bispecific monoclonal antibody, provided sustained retinal stability in patients with diabetic macular oedema (DMO) compared with other retinal treatments.

In preclinical studies, blocking angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF-A) reduced the vascular leakage/neovascularization, inflammation, and fibrosis.

In a phase 2 post hoc analyses, the investigators assessed, in the intention-to-treat population, the sustained retinal stability, defined as occurrence and less than 10% worsening of the central subfield to 325 microns or less to week 24. The inflammatory biomarker, intercellular adhesion molecule-1 (ICAM-1), levels also were assessed in a patient subset from baseline to week 28.

The investigators reported that more than 50% of patients achieved sustained retinal stability at weeks 8 and 16 with faricimab compared with week 20 with ranibizumab (Lucentis, Genentech). At week 28, the mean percentage of the ICAM-1 levels compared with baseline increased by 50% with ranibizumab and decreased by 56% and 42% in the 2 faricimab arms.

The investigators concluded that faricimab resulted in sustained retinal stability and ICAM-1 reduction compared with ranibizumab in the phase 2 study. In addition, in the phase 3 studies, faricimab showed greater anatomic improvement compared with aflibercept (Eyelea, Regeneron) and potential for improved durability due to vascular stability by Ang-2 inhibition.

Faricimab is the only medicine targeting two distinct pathways, Ang-2 and VEGF-A, that often cause retinal diseases that may cause vision loss.

During a presentation at the American Academy of Ophthalmology 2021 annual meeting in New Orleans, Dr Veeral Sheth presented research that found faricimab, a bispecific monoclonal antibody, provided sustained retinal stability in patients with diabetic macular oedema (DMO) compared with other retinal treatments.

Metabolomics, defined as the qualitative and quantitative analysis of metabolites <1-1.5 kilodaltons, may be able to contribute to the understanding age-related macular degeneration (AMD) progression and the identification of patients at higher risk for progression, according to Dr Ines Lains from Mass. Eye and Ear, Harvard Medical School, Harvard University, Boston.

Speaking at the American Academy of Ophthalmology 2021 annual meeting in New Orleans, Dr Lains explained that the mechanisms of AMD progression currently remain poorly understood and the tools to predict and halt progression are limited. Previous work, both by our group at MEE and others, have shown that plasma metabolomic profiles of patients AMD differ from controls. So far, no follow-up studies have been done. This study, for the first time, examined the association between metabolomics and AMD progression in a longitudinal study.

Longitudinal study of plasma metabolomics in AMD

Dr Lains and the team, under guidance of Drs Joan W. Miller and Deeba Husain, conducted a prospective longitudinal study to analyse the associations between baseline plasma metabolomic profiles and AMD progression at 3 years.

The main outcomes measures were AMD progression as documented in colour fundus photographs (retinal structure) and changes in time to dark adapt (retinal function).

A total of 153 eyes were included in the study: of these, 26 with progression of AMD at 3 years.

The analyses showed that 8 metabolites were associated with AMD progression based on colour fundus photographs, with an enrichment of the pentose and glucoronate interconversions pathway. Additionally, metabolites in the alanine, aspartate and glutamate pathway were associated with 3-year changes in dark adaptation.

“In this study we observed that baseline plasma metabolomic profiles are associated with progression of AMD at 3 years,” Dr Lains said. “In particular, the identified metabolites and metabolomic pathways are related to oxidative stress, suggesting that it may play a particularly important role in the progression of AMD both at structural and functional levels, as measured by dark adaptation.”

Dr Lains concluded that the findings contribute to our understanding of mechanisms of AMD progression as well as the development of future biomarkers and potential therapeutics for this blinding disease.

Dr Lains reported no financial disclosures related to this content.

Speaking at the American Academy of Ophthalmology 2021 annual meeting in New Orleans, Dr Ines Lains explained that the mechanisms of AMD progression currently remain poorly understood and the tools to predict and halt progression are limited.

Dr Cathleen McCabe sits down with Sheryl Stevenson of 

 to discuss the recently FDA-approved drops, VUITY. At AAO 2021, her presentation entitled, "GEMINI 1 and 2 pooled Phase 3 safety and efficacy: AGN-190584 primary and key secondary endpoints," discussed the finer points of the clinical trial that led to VUITY's early approval.

Allergan, a subsidiary of AbbVie, announced on October 29, 2021, that the US Food and Drug Administration (FDA) has approved pilocarpine HCl Ophthalmic Solution 1.25% for the treatment of adult patients with presbyopia.

Pilocarpine HCl ophthalmic solution 1.25% is the first and only approved eye drop to treat age-related blurry near vision.

At AAO 2021, Dr Ajay Kuriyan presented his poster, "Fluctuations in central subfield thickness associated with worse visual outcomes in patients with diabetic macular oedema [DMO] in clinical trial setting." This data was previously presented as a talk at the ASRS 39th Annual Scientific Meeting.

Dr Kuriyan practices at the Wills Eye Institute. He is also assistant professor of ophthalmology at Sidney Kimmel Medical College at Thomas Jefferson University.

An epidemiologic analysis of malignant ocular surface tumours, which are rare but serious events, found significant differences in geographic prevalence rates in the US with more Caucasian men and smokers affected, according to Nathan Hall, MS, BS, from the Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston.

Considering the seriousness of these tumours of the conjunctiva and/or cornea, patient morbidity and mortality can be affected, Hall pointed out, noting the importance of identifying the associated risk factors, such as ultraviolet light exposure in various regions, gender, and older age that can play a role.

Hall and his colleagues conducted the analysis, which used data from the American Academy of Ophthalmology’s IRIS Registry, and included more than 15,000 patients who had been diagnosed with a malignant ocular surface tumour of the conjunctiva/cornea between 2013 and 2019.

The investigators found that prevalence rates of ocular surface tumours differed across all geographic areas, with the highest prevalence in the North Central region (0.0032 cases/100,000) and lowest in the West (0.0014 cases/100,000), Hall reported.

Investigators found that prevalence rates of ocular surface tumours differed across all geographic areas. (Image courtesy of Nathan Hall, MS, BS)

White males and smokers were most highly affected and non-white females were the least affected (p < 0.0001 for all comparisons). Hall also noted that smoking seems to have an impact on the prevalence because the investigators found a significantly higher proportion of current smokers within those patients with an ocular surface tumour than in the general IRIS Registry patient pool.

Investigators also pointed out that exposure to ultraviolet light and latitude-related differences have been reported previously as risk factors for ocular surface tumours in other studies, and including similar types of data in the IRIS Registry should be another path of investigation.

“Our results suggested a significantly higher prevalence of ocular surface tumours in white males and smokers, and differences between geographic area of the US,” Hall concluded.

In a presentation at the American Academy of Ophthalmology’s 2021 annual meeting in New Orleans, Nathan Hall pointed out that an epidemiologic analysis of malignant ocular surface tumours found significant differences in geographic prevalence rates in the United States.

Ocular findings in infants with congenital Zika virus syndrome (CZS) were similar among the affected infants and occurred frequently, according to Dr Denise Freitas, who presented findings at the American Academy of Ophthalmology 2021 annual meeting in New Orleans.

The most prevalent of the findings was optic nerve pallor.

Dr Freitas is from the Department of Ophthalmology and Visual Sciences, Paulista School of Medicine, Hospital São Paulo, and the Federal University of São Paulo, São Paulo, Brazil.

Dr Freitas and colleagues conducted a study to characterize the ocular findings in infants with microcephaly and CZS from 2015 to 2017 in Paraiba, Brazil.

The investigators classified the infants into 1 of the following 3 categories: confirmed congenital ZIKV infection based on a positive test and negative for rubella, toxoplasmosis, HIV, syphilis, cytomegalovirus, and herpes simplex virus; probable congenital ZIKV infection, indicating a previous ZIKV infection or passive immunity and negative tests for the other infections; or suspected ZIKV infection in infants that did not undergo testing for ZIKV or other disease but exhibited clinical findings suggestive of the congenital ZIKV syndrome, Dr Freitas explained.

Fifty-six infants were included in the study, all of whom had microcephaly and other signs that are typical of CZS. The mean age at examination was 5.25 months (median, 4 months; range, 1-12 months). The mean head circumference was 28.76 centimetres (median, 29 centimetres; range, 25-31.9 centimetres).

Dr Freitas reported that 12 (21.4%) infants had confirmed congenital ZIKV infection, 15 (26.8%) had probable infection, and 29 (51.8%) had suspected infection.

Ocular findings were identified in 24 infants (42.9%) of the 56 infants and included gross retinal pigmentation in 11 (45.8%), macular chorioretinal atrophy in 11 (45.8%), optic nerve hypoplasia in 1 (4.2%), optic nerve pallor in 14 (58.3%), and increased optic disc excavation in 2 (8.3%).

“The ocular findings were similar among the infants and consistent with those reported in the literature, regardless of the patients’ serologic confirmation or classification,” Dr Freitas concluded. “The findings were identified frequently and the prevalent was optic nerve pallor.”

During a presentation at the American Academy of Ophthalmology 2021 annual meeting, Dr Denise Freitas reported that the ocular findings in infants with congenital Zika virus syndrome were similar among the affected infants and occurred frequently. The most prevalent of the findings was optic nerve pallor.

Autoimmune uveitis comprises a diverse group of diseases that can differ widely in clinical presentation and duration.

 Although a number of systemic autoimmune diseases can manifest as noninfectious uveitis (NIU)—for example, psoriasis, ankylosing spondylitis, multiple sclerosis, sarcoidosis, and ulcerative colitis—many cases of NIU are idiopathic. Indeed, in the US, most uveitis is of noninfectious or autoimmune origin, with a majority of those cases being idiopathic.

The autoimmune mechanisms at work in the pathogenesis of uveitis are not completely understood; but it is known that the retina contains several potent autoantigens that are expressed in the thymus and secondary lymphoid tissue, where immunological tolerance is maintained. Regulatory T cells, which help maintain self-tolerance and control immune responses, are also present in the retina.

 In the context of an autoimmune disease, local dynamics of immune cell trafficking within the eye may be altered, and the resulting remodelling may put the eye at risk of nonspecific immune activation, precipitating clinical signs of inflammation.

Uveitis is categorized anatomically as anterior, intermediate, posterior, or panuveitis, with symptoms that generally correspond to the location of inflammation. When the inflammation predominantly affects the anterior segment, patients may experience pain, sensitivity to light, and redness; posterior-segment inflammation can result in floaters, flashes, blurry vision, and blind spots. Although patients with posterior uveitis may not experience pain, it is generally the most dangerous in terms of vision, as choroidal inflammation and its resultant scarring can affect the retina, optic nerve, and macula very quickly.

In my experience, it is common for patients with NIU to present to the clinic without a previous diagnosis of systemic autoimmune disease; typically, they have experienced some worrisome vision loss or irritation that prompts their visit. They may, however, have other extraocular symptoms that they have been neglecting, such as joint pain (inflammatory joint pain is typified by exacerbation following a period of inactivity, such as wakening in the morning), nail pitting, or hair loss. Every patient new to our practice is asked to complete a 

 to help uncover ocular and systemic symptoms that he or she may not otherwise think to report.

In terms of ocular findings, diagnosis of anterior uveitis is relatively straightforward at the slit lamp; in cases of posterior-segment involvement, imaging tools such as optical coherence tomography (OCT), fluorescein and indocyanine green angiography, and fundus autofluorescence are essential adjuncts. For certain uveitic entities, visual field testing and electroretinogram can be helpful. In general, the diagnostic workup for a patient with NIU often requires time, consideration, and collaboration with other specialists. In addition to review of systems and ocular exam, we do bloodwork to rule out infection and help identify signs of systemic autoimmune activity (e.g., HLA haplotyping, antinuclear antibodies, serum angiotensin-converting enzyme, lysozyme, to name a few). Even when a systemic workup is negative for infection or clearly defined autoimmune disease, patients can be comforted that we still have effective ways of managing uveitis that is presume autoimmune, noninfectious in nature.

Our knowledge of ocular immunology has grown immensely over the past decade or two, revealing a complex web of interconnected pathways, signalling molecules, and surface markers involved in acute and chronic inflammation. In treating NIU and other autoimmune-mediated diseases, it is rarely as simple as blocking a single molecule and turning a single switch on or off. Still, in recent years, targeted biologic treatments for autoimmune disease have been approved, including some specifically for NIU.

Humira (adalimumab, AbbVie) is the first FDA-approved biologic therapy for noninfectious uveitis affecting the posterior segment. Most of the other systemic immunosuppressive therapies used to treat uveitis are off-label, including methotrexate, mycophenolate, azathioprine, and cyclosporine. Although these therapies have been used for many years, they do not have FDA approval for this indication and lack the support of randomized controlled trials.

Through clinical experience, we know that these are excellent steroid-sparing medications. Although these therapies are well accepted today, in the past, many considered them as overly aggressive. Now, uveitis has become a “mainstream” subspeciality, and fellows at many respected academic and private institutions are well trained in the use of systemic therapies. In addition, physicians tend to refer patients to uveitis specialists much earlier than in the past, which lowers patients’ exposure to systemic steroids and their associated side effects.

In and out of specialists’ practices, however, steroids are still the mainstay of treatment because rapid control of inflammation is essential to preserving vision.

For patients with NIU and a well-defined systemic autoimmune disease, systemic treatment is usually the best choice to control disease throughout the body. The question of systemic vs local treatment becomes more controversial if, after doing a head-to-toe work-up, the patient only manifests NIU and no other complaints. In such cases, it may make sense to treat systemically if the uveitis is bilateral, but perhaps locally if unilateral (but that ultimately depends on the specific diagnosis).

Local treatments for NIU are largely corticosteroids, though intraocular injection of agents such as sirolimus and methotrexate have been studied.

 Key considerations for local therapy include age and lens status, as well as individual or family history of glaucoma or steroid-induced ocular hypertension. A very young phakic patient, or one with numerous risk factors for glaucoma, may not be a good candidate for local corticosteroid therapy. On the other hand, patients who are pregnant or trying to conceive, or those who are immunocompromised, may be poor candidates for systemic therapy. Recently, even those with only a theoretical risk of compromised immunity (e.g., due to age or recent recovery from cancer) are often reluctant to undergo systemic immunosuppression because they fear the SARS-CoV-2 infection.

Current approved options for local therapy include topical steroids, shorter-acting intra- and periocular steroids, such as triamcinolone acetonide, and sustained-release intravitreal implants, including Ozurdex (dexamethasone intravitreal implant 0.7 mg, AbbVie) and YUTIQ (fluocinolone acetonide intravitreal implant 0.18 mg, EyePoint Pharmaceuticals). Ozurdex is typically effective for about 3 to 4 months when used to treat uveitis, while YUTIQ releases a consistent low dose of fluocinolone for 36 months. The surgically implanted Retisert (fluocinolone acetonide intravitreal implant 0.59 mg, Bausch + Lomb), which also lasts about 36 months, is generally reserved for more severe presentations in which a higher dose of steroid is warranted.

I usually bring patients on systemic immunosuppressive therapy back for follow-up every 2 to 3 months to examine the eyes for signs of recurrent inflammation and perform blood testing to ensure the efficacy and safety of the therapy. For patients who receive local, sustained-release steroid treatment such as YUTIQ and Retisert, I also follow them every 3 months to monitor intraocular pressure.

We can expect the future of immune-mediated uveitis to feature increasingly targeted and specific therapies, including more biologics and biologic response modifiers, both systemically and locally in the eye. In the immediate term, we can look forward to the suprachoroidal formulation of triamcinolone (Xipere, triamcinolone acetonide suprachoroidal injectable suspension, Bausch + Lomb)

, which may offer a more targeted impact on uveitic macular oedema with fewer adverse events of IOP elevation and cataract development than other intra- and periocular steroids. We may also see the approval of intravitreal sirolimus (Santen), which would offer a local, non-steroid option.

Case study: Preserving systemic immune function

I recently saw a 50-year-old man with metastatic melanoma, which was being successfully treated with immunotherapy. However, as a consequence of the immunotherapy, he had developed bilateral panuveitis, a side effect that has been reported with immune-checkpoint inhibitors.

 To avoid disrupting the patient’s systemic cancer care, we elected to treat the uveitis locally with YUTIQ following an incomplete response to topical steroid.

The patient experienced improvement in vision following YUTIQ injection and at about 18 months post-treatment, he remains 20/20 in both eyes. He did develop cataract, but is happy with his vision following surgery. Intraocular pressure (IOP) elevation, also secondary to YUTIQ, is well controlled on a single IOP-lowering drop.

In a 3-year, phase 3 clinical trial, patients who received YUTIQ experienced a statically significantly lower rate of uveitis recurrence compared to the sham/standard of care treatment arm (

 YUTIQ also resulted in greater resolution of macular oedema and greater improvement in visual acuity.

 IOP-lowering medications were used at similar rates, but more patients in the sham/standard of care group received IOP-lowering surgeries.

This case illustrates the important interaction between systemic immunity and ocular inflammation, and the value of long-term, local inflammation control.

Dr. Chang is Co-President and Partner at Massachusetts Eye Research & Surgery Institution (MERSI) in Waltham, MA. He specializes in ocular inflammatory disease and vitreoretinal surgery.

Caspi RR. Understanding autoimmune uveitis through animal models. The Friedenwald Lecture. 

Lee RW, Nicholson LB, Sen HN, et al. Autoimmune and autoinflammatory mechanisms in uveitis. 

Forrester JV, Kuffova L, Dick AD. Autoimmunity, Autoinflammation, and Infection in Uveitis.

Holland GN, Goldstein DA, Rosenbaum JT, Van Gelder RN. MD roundtable: the uveitis workup. 

https://www.aao.org/eyenet/article/md-roundtable-uveitis-workup

Knickelbein JE, Kim M, Argon E, Nussenblatt RB, Sen NH. Comparative efficacy of steroid-sparing therapies for non-infectious uveitis. 

Nguyen QD, Merrill PT, Sepah YJ, et al. Intravitreal sirolimus for the treatment of noninfectious uveitis: evolution through preclinical and clinical studies. 

Taylor SR, Banker A, Schlaen A, et al. Intraocular methotrexate can induce extended remission in some patients in noninfectious uveitis. 

Yeh S, Khurana RN, Shah M, et al. PEACHTREE Study Investigators. Efficacy and safety of suprachoroidal CLS-TA for macular edema secondary to noninfectious uveitis: phase 3 randomized trial. 

Shahzad O, Thompson N, Clare G, et al. Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm. 

Sharma S. Best corrected visual acuity at 36 months in a study of fluocinolone acetonide intravitreal (FAi) insert for non-infectious uveitis affecting the posterior segment of the eye (NIU-PS). Presented at the ASRS annual meeting, Chicago, IL; July 26-30, 2019.

Hariprasad SM, Patel K. Course of macular edema through 36 months with fluocinolone acetonide intravitreal insert for noninfectious uveitis affecting the posterior segment. Presented at the American Society of Retina Specialists 38th annual scientific meeting. July 24-26, 2020 (virtual).

Singer MA, Krambeer C, Paggiarino D. IOP elevation in patients treated with fluocinolone acetonide insert for chronic noninfectious uveitis affecting the posterior segment. 

Ophthalmic Surgery, Lasers and Imaging Retina

Underlying autoimmune disease alters uveitis therapy.

Current approaches to treatment of uveitis with autoimmune disease

Anti-VEGF therapies have been highly beneficial for patients with macular degenerations, but these patients require frequent treatment to maintain visual acuity, underscoring the need for sustained-release products, according to Dr Lejla Vajzovic, an associate professor of ophthalmology at Duke University Eye Center in Durham, North Carolina.

Dr Vajzovic discussed the 2 surgical options that facilitate increased durability for patients with retinal degenerations for exudative age-related macular degeneration (AMD).

The Port Delivery System (PDS) (Susvimo; Genentech), a recently FDA-approved drug delivery system, is a permanent refillable intraocular implant that is positioned at the pars plana. The device contains a customized formulation of ranibizumab (Lucentis; Genentech) that can be refilled in the office.

The Phase 3 ARCHWAY study of patients with wet AMD showed a favourable benefit-risk profile for the PDS. The change in best-corrected visual acuity at weeks 36 and 40 was comparable to that achieved with monthly ranibizumab injections. This approach was able to maintain the visual acuity with a reduced treatment burden.

Dr Vajzovic emphasized the importance of strict adherence to the surgical steps during PDS implantation: peritomy, implant preparation, scleral dissection, pars plana laser ablation and incision, implant insertion, and conjunctival and Tenon’s capsule closure.

“Control of haemostasis is critical at all steps to ensure optimal visualization and minimize the risk of postoperative vitreous haemorrhage,” she said.

Precise handling of the conjunctiva and Tenon’s capsule and anchoring both to the limbus during closure are crucial to optical outcomes, Dr Vajzovic pointed out. Proper handling ultimately results in decreased risks of exposure and infection. Scleral dissection followed by laser ablation of the pars plana reduces the chances of intraocular bleeding.

The office refill procedure necessitates precise perpendicular targeting using a needle that both injects new drug and excretes the fluid that fills the implant.

Dr Vajzovic provided 4 key points about PDS insertion:

The sclera is incised layer by layer to expose the pars plana, followed by pars plana laser ablation incision. The incision size is maintained at 3.5 mm to ensure the secure fit of the implant and pars plana haemostasis.

The conjunctiva and Tenon’s capsule are manipulated with care and anchored to the limbal sclera using a slight overapproximation, which is critical for the implant to stay covered.

Control of haemostasis is critical at all stages of the implantation to minimize vitreous haemorrhages.

During the refill/exchange procedure, the surgeon stands on the contralateral side of the study eye, using a perpendicular approach and precise targeting.

The ranibizumab PDS implant received FDA approval in October 2021 following positive Phase 3 results.

RGX-314 is a novel adeno-associated virus vector used to deliver an anti-VEGF drug that has shown favourable results in Phase 1/2a neovascular AMD studies. The study tested 5 doses administered to patients who previously required frequent injections. The subretinal dosing to date has been completed in 42 subjects in dose-escalating cohorts. The patients were followed up to 2 years.

This procedure involves a vitrectomy followed by subretinal injection of the device with subsequent bleb formation. The patients generally required only a subconjunctival steroid injection.

Dr Vajzovic related the case of an 86-year-old patient randomized to the highest tested dose who did not require further injections after the injection and experienced a small, stable visual improvement.

The interim conclusions drawn from the results were that RGX-314 was well tolerated by all patients and that the treatment provided a long-term, durable treatment effect seen with the 3 highest doses. The patients in the 2 highest-dose cohorts have been followed for more than 1.5 years with stable to improved vision and reductions in the treatment burden. Those in cohort 3 who were followed for more than 3 years had the same results. The pivotal trial, ATMOSPHERE, is now enrolling patients.

RGX-314 is also being evaluated for suprachoroidal use in a Phase 2 neovascular AMD study, and the interim data are expected to be released the third quarter of 2021. A Phase 2 trial, ALTITUDE, for treatment of diabetic retinopathy is now enrolling patients, and the initial data release is expected this year.

This article is adapted from Dr Vajzovic’s presentation at the Women in Ophthalmology 2021 Summer Symposium. Dr Vajzovic is a consultant to RegenXBio Inc and Roche/Genentech.

Surgical options facilitate increased durability for patients with retinal degeneration.

PDS and RGX-314: Two new surgical procedures for the treatment of wet AMD

The port delivery system is an ocular delivery system that is surgically inserted via the pars plana area in the superotemporal quadrant of the eye. It provides continuous delivery of ranibizumab to the posterior segment. It has a reservoir chamber where a higher concentration of ranibizumab is held, and there is slow release into the vitreous cavity. It has been approved for use in patients with neovascular AMD [age-related macular degeneration], although other indications, including diabetic macular edema, are also being investigated.

With the approval of Lucentis [ranibizumab] for the indications of neovascular AMD, the treatments for neovascular AMD were revolutionized. However, there still is a significant treatment burden for many of our patients who require frequent, often monthly, injections. The treatment burden for both the patients and the family can be quite high. In addition, although we’re delivering a nice bolus of anti-VEGF treatment, there is a waning of the amount of medication in the vitreous cavity. Therefore, a more sustained, endurable treatment modality was needed. Like most devices, the port delivery system was started in the preclinical stages, where it was developed and then tested in nonhuman subjects. Once its safety was verified, it went on to trials to verify safety in human patients, and then to look at the efficacy.

In the phase 2 LADDER study, the technique that was done in human patients initially showed an increased risk for vitreous hemorrhages. The technique for implantation was modified to include laser cautery of the corneal bed]. After this, the incidence of vitreous hemorrhages dropped precipitously. Prior to the amendment, there were 6 out of 10 cases of vitreous hemorrhage. After the amendment, there were no cases of vitreous hemorrhage out of 48 patients within the first month, which is generally considered the postoperative period. At 2 months, there was 1 patient who did have a vitreous hemorrhage.

Although the procedure is generally well tolerated, since it is surgical procedure, there are some potential complications that surgeons and patients should be aware of. Initially, in the LADDER study, there was a higher rate of vitreous hemorrhages. A modification of the procedure has since reduced those rates tremendously. Any surgery has a risk of infection, and with respect to the implant itself, if the conjunctiva is not closed properly or not covering the implant adequately, there is a possibility of the implant being exposed. Also, if the conjunctiva is very thin, there is a possibility of erosion. Therefore, presurgical evaluation and meticulous care to close the conjunctiva are very important.

When evaluating a patient preoperatively, you want to take note of a few things. Particularly, you want to take note of the conjunctiva to see if it’s very thin, and if there’s good mobility of the conjunctiva, so that you can adequately access the subconjunctival and sub-Tenon space. In addition, you also want to note any areas of potential scleral thinning, so that when you’re making your wound you’re aware, and so you don’t start making your wound too deep. In addition, you may also want to avoid those areas, so that there isn’t a risk of dehiscence or any other potential issues with the wound.

Expert insight on the history of the port delivery system in neovascular AMD and how it has impacted patient experience and outcomes.