Cheryl Guttman is a medical writer based in Deerfield, Ill.

Cheryl Guttman Krader, BS, Pharm

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This article was reviewed by Judy E. Kim, MD



Many imaging modalities are available for ophthalmologists to use in clinical care, but whether a specific technology is essential for individual clinicians depends on a variety of factors, according to Judy E. Kim, MD.

Kim, a professor of ophthalmology and director of teleophthalmology at the Medical College of Wisconsin in Milwaukee. 

She also offered her perspectives on how the features influence whether a particular device might be deemed a “need” versus a “want” for ophthalmologists in different practice situations.

“The discussion of determining whether anything is a need versus a want centers on 1 issue: Is it essential or just something that is desired or wished for,” she said. “However, the definition of essential is subjective and differs in different situations.”

Kim pointed out that with imaging devices, as in life, ophthalmologists have to prioritize their needs and wants.

“It can be a tricky balancing act that involves weighing what is necessary to provide best care for patients versus the cost, ease of use, accuracy, and the additional information provided by the device along with the needs of other clinicians in a practice, among many other considerations,” she explained.


The needs for imaging modalities vary between general ophthalmologists and different subspecialists. 

As a retina specialist, Kim said that if she had to choose just 1 imaging modality, it would be spectral domain (SD) OCT. SD OCT platforms generate high-resolution cross-sectional and 

 images of the retina, anterior segment, and optic nerve head.



OCTA a hope for diagnosing, managing ophthalmic diseases

This noninvasive imaging modality has revolutionized the diagnosis and management of retinal diseases by providing information that is often not readily visible on clinical evaluation.

Swept-source (SS) OCT is a newer technology that affords better imaging of the choroid and vitreous, improved imaging through blood and media opacity, and a wider field of view compared with SD-OCT.

However, Kim classified SS-OCT as a want rather than a need because of its cost and the fact that the information provided by SD-OCT currently suffices for patient management.


Ultrasound is not often used by retina specialists, but Kim still considered it a need because it allows visualization of the posterior segment when other imaging is not possible. 

As a result, it allows diagnosis of retinal detachment, intraocular foreign body, posterior scleritis, optic nerve head drusen, and other issues. 

It is also essential for ocular oncologists, who use it more often to differentiate various types of tumors and to monitor for tumor growth, but it may not be essential for general ophthalmologists, she said.

Although some ophthalmologists feel there is no longer a need for color fundus imaging, Kim said she still finds it useful for documentation and education. However, she is relying more on widefield and ultra-widefield systems that image between 50º and 200º field, respectively.



FAF shedding light on patterns related to disease chronicity in CSC

“Why limit ourselves to a small field of view when we can see so much more with widefield or ultra-widefield imaging,” she said, adding that being able to image a widefield with a single shot is useful for imaging children, who often cannot sit for long periods.

As a major benefit, ultra-widefield imaging allows documentation and evaluation of a multitude of retinal conditions that affect the periphery as well as the posterior pole.

Furthermore, whereas images acquired with conventional fundus cameras can be suboptimal in eyes with small or undilated pupils, systems that utilize confocal scanning laser ophthalmoscopy can photograph the peripheral retina in eyes with pupil diameters as small as 2.5 mm.

“Imaging through an undilated pupil may be especially useful for teleretinal screening and for allowing faster flow of patients in the clinic, which has become especially important during the [coronavirus disease 2019] pandemic,” Kim said.

“In addition, several studies have established the equivalence in sensitivity between nonmydriatic ultra-widefield scanning laser ophthalmoscopy images and dilated [Early Treatment Diabetic Retinopathy Study] standard 7-field stereo photographs for evaluating the severity of 

,” she said. “Being able to see [farther] out to the peripheral can improve staging and diagnosis.”



OCT: Illuminating the retina layer by layer

Kim said she considers ultra-widefield fundus fluorescein angiography (FA) to be another essential tool for managing patients with retinal vascular disease.

According to Kim, for most ophthalmologists, fundus autofluorescence (FAF) may be desirable but not essential.

She explained that FAF is a useful modality for assessing progression of geographic atrophy in patients with dry age-related macular degeneration and for studying and managing eyes with rare inherited retinal degenerative diseases. 

In addition, FAF is useful adjunctive imaging to SD-OCT as a screening tool for hydroxychloroquine toxicity because it can detect early as well as late stages of this condition.

“For Asian patients, widefield fundus autofluorescence may be useful given evidence that changes in the paracentral macula may be present early in the development of hydroxychloroquine toxicity within this racial group,” Kim noted.




OCT angiography (OCT-A) is another type of OCT that allows noninvasive visualization of retinal and choroidal vessels without the use of intravenous dye. It is ideal for patients who are allergic to fluorescein dye or who are pregnant. 

Compared with FA, evaluation of the foveal avascular zone and different layers of blood vessels are improved with OCT-A.

The fact there is no leakage of dye with OCT-A may make visualizing retinal neovascularization more difficult compared with conventional FA, and this newer technology is also hampered by variable image quality, smaller field of view, and difficulty in interpretation. 

Together these issues make OCT-A more of a want than a need, Kim said. “Of course, swept-source devices can provide an unparalleled field of view with OCT-A, but still cost is a deterrent,” she said.


“We now have many imaging options that allow us to visualize the retina [as] never before, and more innovations are expected in the future,” Kim said. “Each physician and the practice should evaluate which imaging modalities and what combination of these in a device will best serve the patients and the practice.” 

e: jekim@mcw.edu
This article is based on a presentation from the American Academy of Ophthalmology’s virtual 2020 annual meeting that provided an overview of the capabilities and limitations of a number of imaging modalities.


Kim receives research support from Optos.

Articles

Physicians should evaluate which options best meet the needs of their practices.

Do you 'need' or just 'want' that new diagnostic imaging device?

, voretigene neparvovec-rzyl (Luxturna, Spark Therapeutics), was approved by the FDA in 2017. 

More than 3 years later, the field has a rapidly changing horizon, according to Christine Kay, MD.

“The standard of care for inherited retinal diseases has been elevated to a new level, requiring early diagnosis, genetic testing, and familiarity with clinical trials so that we can correctly counsel our patients,” said Kay, a retina specialist with Vitreo Retinal Associates in Gainesville, Florida, and an affiliate assistant professor of ophthalmology at the University of South Florida in Tampa.

Kay provided an overview of gene therapy and discussed current gene therapy clinical trials and patient counseling pearls for selected inherited retinal diseases.

Research is unfolding the proteins in retinitis pigmentosa


Gene therapy for retinal dystrophies involves several different techniques that vary depending on the type of mutation. 

For recessive diseases in which the goal is to replace a missing function, the therapy is based on an augmentation (replacement) strategy. 

In contrast, for dominant diseases in which the mutation is causing protein misfolding or toxicity, gene therapy aims to suppress or inactivate the toxic gene.

 Strategies include using short synthetic single-stranded oligonucleotides that can alter RNA, and CRISPR gene editing to manipulate DNA in vivo, said Kay.

For multifactorial diseases such as age-related macular degeneration, for which there is no single underlying genetic cause, gene therapy can provide an additional means of introducing a therapeutic, such as an anti-VEGF agent. 

Novel gene therapy/medical device combo sheds light on retina in RP

Non–genotype specific gene therapy using neuromodulation or optogenetics is an approach employed when the causative gene for a disease is not known. Its goal is to genetically alter ganglion cells to increase their photosensitivity.


Clinical care and clinical trials for retinal diseases


Multiple clinical trials of therapeutics for Stargardt disease are ongoing. These include a lentivirus gene therapy trial, a stem cell therapy trial, studies investigating orally administered drugs—one evaluating a chemically modified vitamin A and another examining a visual cycle modulator—and a study of an intravitreal complement inhibitor.

According to Kay, genetic testing is critical for patients with Stargardt disease and should be done to confirm mutations in the 

In addition, physicians should advise patients to avoid supplemental vitamin A and protect their eyes in sunlight. 

Counseling should also include a discussion of “Fishman’s rule” that gives patients an idea of their disease’s natural history.

Investigators uncover improved vectors for ocular gene therapy

“Vision can decline slowly until acuity reaches 20/40, at which point there is typically a 7- to 10-year period of decline to reach the typical end stage of 20/200,” Kay said.

Current gene therapy trials for Leber congenital amaurosis (LCA) include one involving antisense oligonucleotide therapy and another using a CRISPR system for gene editing. Kay noted that LCA is often misdiagnosed as retinitis pigmentosa (RP).

“Clinicians should ask about congenital onset and nystagmus and be aware of a possible association between LCA and the autism spectrum as well as misdiagnosis with these patients,” she said.

CNGB3-achromatopsia is another disease for which there are ongoing gene therapy trials. It can mimic blue cone monochromacy, Kay said, although patients with the latter typically have slightly better acuity and a better result on the Farnsworth-Munsell 100 Hue Color Vision test. 

It is possible to distinguish between the 2 conditions by using electroretinography or, more easily, genetic testing. 

To address the exquisite photosensitivity or photoaversion associated with achromatopsia, Kay recommended that patients wear red-tinted lenses.

Ocular gene therapy offers hope for inherited retinal disease

Representing a progressive, later-onset, diffuse photoreceptor disease, RP is relatively common, with a prevalence of 1 in 4000 individuals. 

Kay said that patients with RP should have genetic testing to identify the underlying mutation that will determine their candidacy for ongoing clinical trials. 

In addition, physicians should monitor these patients for cystoid macular edema (CME) using optical coherence tomography.

“CME is common in patients with RP and should be treated with carbonic anhydrase inhibitors as first-line therapy as well as with steroidal and nonsteroidal therapy to preserve the foveal structure,” Kay said.

Regarding other retinal diseases, investigators are examining antisense oligonucleotide therapy for the treatment of Usher syndrome due to mutations in exon 13 of the 

 gene. Choroideremia is also the subject of multiple ongoing gene therapy trials.

Gene panel offers expanded diagnostic capability of inherited retinal diseases

Further, the National Eye Institute is the sponsor of a gene therapy trial for gyrate atrophy. 

According to Kay, genetic testing is not necessarily needed for diagnosing this condition, which can be ruled in or out based on the serum ornithine level. 

A finding of elevated ornithine also informs a decision about vitamin B therapy, she said. 


This article is based on Kay’s presentation at the American Academy of Ophthalmology 2020 virtual annual meeting. Kay is a consultant and/or investigator for multiple companies developing retinal gene therapies. She holds equity in Atsena Therapeutics and receives honoraria from the Bascom Palmer Eye Institute as a member of the data safety monitor board for a choroideremia trial.

Physician offers patient counseling pearls for selected retinal diseases.

Gene therapy heralds new era for inherited retinal diseases

This article was reviewed by Steven T. Charles, MD

Differences in surgeon preferences and perceptions may make some issues in vitreomacular surgery seem controversial, according to Steven T. Charles, MD, who addressed topics in macular surgery and shared his evidence- and expert-based insights for achieving best outcomes.


Outlining his indications for internal limiting membrane (ILM) peeling, Charles said he does it in all cases involving lamellar or full–thickness macular holes, epimacular membranes, vitreomacular schisis, and vitreomacular traction, including diabetic macular edema. 

Autologous retinal transplant for larger macular holes gaining traction



He also performs ILM peeling in vitreomacular traction syndrome, eyes with macular folds inadvertently created after a suboptimal fluid-air exchange, and in hypotony maculopathy cases, for which he credited Jeroni Nadal, MD. 

In addition, Charles said he often peels the ILM when operating for diabetic traction retinal detachments (TRDs), after finding it enables better smoothing of macular folds.

“ILM peeling has many advantages,” said Charles, founder of the Charles Retina Institute in Germantown, Tennessee. “On the table, it instantly eliminates striae and guarantees complete removal of residual vitreous cortex and epimacular membranes.”

The peeling is done via a pinch peeling technique performed using an end-grasping forceps and mandates an excellent view and depth control. 

The pinch peeling technique, which Charles developed 40 years ago, has benefits for greater efficiency and safety compared with other approaches, he said.

“Inside-out, end-grasping ILM pinch peeling eliminates the need for using any other instruments to start the peel,” he explained. “Finding or creating an edge with a bent MVR blade or a forceps with 1 blade under the epiretinal membrane can damage the nerve fiber layer.”

Micro vacuum pick for vitreoretinal surgery may be a better mousetrap

Brilliant Blue G 0.025% ophthalmic solution (Dutch Ophthalmic Research Center) is his dye of choice for staining the ILM. Approved by the FDA at the end of 2019, Brilliant Blue G has many advantages compared with indocyanine green (ICG), Charles said.

“I believe that Brilliant Blue G is the only safe and effective ILM staining agent,” he said. “Unlike ICG, Brilliant Blue G dissolves in balanced salt solution (BSS), not water. It does not fluoresce, and so it poses less risk of phototoxicity, it has a stable pH, osmolarity is not an issue, infusion under air or mixing with dextrose are not necessary.”


Charles said achieving an optimal view for macular surgery requires use of a high quality plano corneal contact lens that will eliminate all corneal asphericity and provide the best resolution. 

Although a noncontact wide-angle viewing system (eg, BIOM, EIBOS) can be acceptable in eyes with a perfect cornea, noncontact visualization does not reduce lateral and axial resolution.

Macular OCT imaging is vital in work-up of cataract surgery patients

“Surgeons working without an assistant should choose a self-adhering plano contact lens rather than one with a handle,” Charles recommended.

He cautioned that increased foveal thickness after successful epimacular membrane and ILM peeling is often misdiagnosed as edema and subsequently treated inappropriately with intravitreal steroid injections that cause harm, inducing cataract and glaucoma.


Charles refuted the idea that vitrectomy causes cataract. He said vitrectomy uniformly causes progression of nuclear sclerosis, acting through a mechanism involving increased oxygen tension in the vitreous cavity. 

He argued against routine phacoemulsification in eyes needing vitrectomy. 

“Numerous clear lenses that still have 10 to 20 years of accommodation left are removed, and I am opposed to that because it clearly results in worse refractive outcomes,” he said.

Charles said that 1 month prior cataract surgery is indicated in eyes with a 2+ or greater nuclear sclerotic cataract (NSC) or any posterior subcapsular cataract. He advocated for 2 procedures with the sequence depending on cataract type.

Challenges to topical drop adherence after cataract surgery


Vitrectomy is done first in the case of a 2+ NSC and followed 1 month later by phacoemulsification and IOL implantation. If the cataract is greater than 2+ nuclear sclerotic or posterior subcapsular, then the lens removal/IOL implantation is done first.


Charles said he believes surgery for lamellar macular holes is indicated if the patient is symptomatic or there is structural damage. 

The goal is to restore normal foveal anatomy and not to prevent progression to a full thickness defect, which is an unpredictable phenomenon.

The procedure must include ILM peeling and staining and use 25% sulfur hexafluoride, not air.

Finally, Charles reported his positive experience in more than 50 cases using an autologous full thickness retinal patch grafts for repair of large macular holes.

 Preventing cystoid macular oedema after cataract surgery

Charles identified Tamer Mahmoud, MD, PhD, as a pioneer of the technique. He said the graft is harvested with scissors just inferior to the inferotemporal arcade and moved to the macular hole under medium-term perfluoro-n-octane (PFO).

The PFO, which is removed after 1 week, is favored over silicone oil because PFO supports graft oxygenation that will promote closure, Charles concluded. 


This article is based on Charles’ presentation at the American Academy of Ophthalmology 2020 virtual annual meeting. Charles is a consultant to Alcon.

Pearls for optimizing patient outcomes of macular surgery

This article was reviewed by Douglas D. Koch, MD



The TECNIS Eyhance and TECNIS Eyhance Toric II IOLs (ICB00/DIUXXX, Johnson & Johnson Vision) were approved by the FDA in early February 2021. 

One week later, Douglas D. Koch, MD, performed the first postapproval cases in the United States using the enhanced monofocal IOL.

Koch said the early results are very impressive and indicate that this new lens technology delivers on its design goals by providing an increased depth of focus that is functionally beneficial.

Extended depth-of-field IOLs: Clarifying current nomenclature

“It is, in effect, an enhanced monofocal 

 that often gives patients something for nothing,” he said. “If my initial patients’ outcomes are replicated as my case series grows, I expect that the [these] IOLs will become my implants of choice in cases where patients are not opting for a presbyopia-correcting lens.”

Koch is a professor and Allen, Mosbacher, and Law Chair in Ophthalmology at Baylor College of Medicine in Houston, Texas.

The enhanced monofocal IOL is a single-piece, aspheric refractive 

 predicated on the platform of the ZCB00 (TECNIS monofocal IOL, Johnson & Johnson Vision). The new lens features the same hydrophobic acrylic material, base geometry, corneal spherical aberration correction, and dimensions as the ZCB00. 

However, the higher-order aspheric anterior surface of the enhanced monofocal IOL creates a continuous increasing progression of power that provides some additional plus power over the central portion.

IOLs offer great vision, low risk profile for myopia

“The novel optic design of the Eyhance results in improved intermediate vision compared with a standard aspheric monofocal

, but [offers] the same performance with respect to distance vision, contrast sensitivity, and risk of photic phenomenon,” Koch said.

Results from a multicenter European prospective randomized study comparing the enhanced monofocal IOL and the ZCB00 IOL demonstrate the performance advantage and safety of the new lens.

 

Patients enrolled in the trial were assigned to undergo bilateral implantation with the enhanced monofocal IOL or the standard monofocal lens; 67 patients who received the enhanced monofocal lens and 72 in the standard monofocal IOL group were seen at a 6-month follow-up visit.

Data from ETDRS visual acuity testing showed the enhanced monofocal

 group achieved significantly better distance-corrected intermediate visual acuity (DCIVA) and uncorrected IVA in both monocular and binocular testing. 

Analyzing the visual, non-visual benefits of VLF IOLs



For all end points, there was a 1.0 to 1.1 line difference (Snellen equivalent) between groups favoring the enhanced monofocal IOL. 

Mean monocular and binocular distance-corrected VA was 20/20 or better with the enhanced monofocal IOL and noninferior compared with the standard monofocal IOL group.

At 6 months in the enhanced monofocal IOL group, mean binocular DCIVA was 20/25 and mean binocular DCIVA was 20/17. Corresponding with the VA results, binocular defocus curves showed better mean VA from -0.5 through -2.0 D for the enhanced monofocal IOL compared with the standard lens.

 were associated with similar results in contrast sensitivity testing. 

In addition, there were no differences between study groups in reports of photic phenomena collected with a symptoms questionnaire nor in adverse event rates.

Visual outcomes of small-aperture IOL implant in post-laser refractive eyes

Study participants also completed the Catquest-SF9, which is a validated questionnaire for assessing vision for daily life activities. The results showed that significantly more patients who received the enhanced monofocal

 reported improvement in their ability to see when walking on uneven surfaces, such as cobblestones.

“This is an interesting finding that is consistent with the larger landing zone and better intermediate vision with the lens,” Koch said.


As a member of the Johnson + Johnson Optics Consulting Group, Koch consulted on the design of the enhanced monofocal lens and was familiar with data from its bench testing. 

With that information and knowing that the lens was being used successfully by some of his European colleagues who have had access to the technology for 2 years, Koch said he was eager to have the chance to implant it.

Aspheric, aberration-free IOL leverages technology for performance

When Koch saw his first 4 patients back for their postop day 1 visit, uncorrected distance and intermediate vision for 3 of the 4 patients who were targeted for distance were 20/20 and J2, 20/25 and J2, and 20/20 and J5, respectively. 

The target refraction for the fourth case was -0.75 D, which was selected to match the fellow eye, and the patient achieved 20/30 uncorrected distance vision and saw J2 for near, he noted.

He added that surgical planning for cases with the Eyhance IOL and implantation is easy.

“The enhanced monofocal IOL has the same A-constant as the ZCB00, and it comes preloaded in the manufacturer’s new injector [Simplicity] that provides the safety and efficiency benefits of a preloaded system, along with very smooth delivery,” Koch said.

Small-aperture single-piece IOL could fill unmet need in patients


In addition to being a promising alternative for cases where a standard monofocal or toric monofocal IOL would be used, the enhanced monofocal IOL and its toric version are options to use in a monovision approach for patients who want an extended range of vision but who don’t want to receive or are not candidates for a specialty presbyopia-correcting IOL. 

In addition, the new lens opens up the possibility of giving an increased depth of focus to patients with ocular comorbidities for whom concerns about reduced contrast sensitivity and visual quality make implantation of an extended depth of focus or trifocal multifocal IOL undesirable.

“I would feel comfortable using the enhanced monofocal IOL in patients with corneal diseases, such as Fuchs' endothelial corneal dystrophy, macular degeneration, or glaucoma,” Koch said.

Assessing aberration of monofocal toric IOL with enhanced optic recovery, alignment

Because of its extended depth of focus, the enhanced IOL also appears to have a broader refractive landing zone compared with a standard monofocal IOL. 

For that reason, Koch said it may be useful in patients who are post-LASIK and for whom accurate calculation of IOL power can still be challenging.

“Patients implanted with the enhanced monofocal IOL will still end up with good distance vision if their refraction ends up +0.4 D,” he concluded. “Surgeons should keep in mind, however, that the benefit of this lens is on the myopic side. Therefore, I recommend aiming for plano or -0.1 D rather than a more myopic target.” 



Koch is a consultant to Johnson & Johnson Vision, Alcon, and Carl Zeiss Meditec.


1. Auffarth GU, Gerl M, Tsai L, et al; Quantum Study Group. Clinical evaluation of a new monofocal intraocular lens with enhanced intermediate function in cataract patients. 

September 3, 2020. doi:10.1097/j.jcrs.0000000000000399

One surgeon shares the early results of his experience using the new TECNIS Eyhance and TECNIS Eyhance Toric II IOLs in performing the first post-FDA-approved cases in the U.S. 

Cheryl Guttman Krader, BS, Pharm

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Do you 'need' or just 'want' that new diagnostic imaging device?