Louise Gagnon

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Ophthalmologists have several options at their disposal for the treatment of presbyopia, according to Dr Elizabeth Yeu, a partner at Virginia Eye Consultants and an assistant professor at Eastern Virginia Medical School in Norfolk. Speaking recently at the virtual 2022 Toronto Cataract Course, Dr Yeu noted that innovation is advancing in presbyopia correction. “We have spent a very long time without much in the way of innovation beyond the realm of glasses and lenses,” Dr Yeu said. “It is a booming field. We know there are a lot of presbyopes worldwide, and the market [for presbyopia management] is huge. It is only growing exponentially.”

There are noninvasive options for presbyopia correction, such as glasses, multifocal contacts, and eye drops. Additionally, surgical options include LASIK, inlays, and refractive lens exchange, Dr Yeu explained. “There [are] a variety of different miotic drops being used, some individually and some in combination [with another treatment],” she said.

The key measurement of efficacy used by the US Food and Drug Administration (FDA) is an improvement in vision of 2 to 3 lines in a 6-hour window, Dr Yeu noted. Some drop options include FDA-approved Vuity, which has pilocarpine as the active ingredient and is a miotic. Brimochol is an investigational treatment that offers near vision improvement and is a combination of carbachol with brimonidine tartrate.

One of the considerations with topical formulations to correct presbyopia is bioavailability. “A better formulation means better bioavailability and a reduced concentration [of the active ingredient] so there are fewer [adverse] effects, [such as] blurred vision, headaches, and brow aches,” Dr Yeu said.

Moreover, another treatment option under investigation in eye drops includes CSF-1 by Orasis Pharmaceuticals, which uses a lower concentration of pilocarpine. PRX-100 is also a miotic therapy, which has aceclidine as an active ingredient. Another novel therapy under investigation is a combination of phentolamine mesylate and pilocarpine, known as Nyxol, which acts as a miotic and vasodilates small muscles, Dr Yeu explained.

One of the novel topical agents is lipoic acid choline ester, which is made to soften the lens and can work in conjunction with a miotic agent to promote accommodation. Another combination to correct presbyopia is True Vision Treatment contact lenses and eye drop kit by Yolia Health, which is a treatment designed to alter the cornea.

Collagen cross-linking may also potentially represent an option in presbyopia correction. “Instead of using it centrally for myopia or keratoconus, if we were to use it in the midperiphery, creating an effective steepening of the centre, this could be used for [patients with presbyopia],” Dr Yeu said, noting that anterior optical coherence tomography images display the central steepening that collagen cross-linking can create.

Synthetic inlays may not be very well tolerated by the human cornea, but allogenic inlays, which are extremely thin, may hold promise, according to Dr Yeu. “If we can get rid of the antigenicity of it, the scaling potential is huge,” she said. “There can be a 3-line improvement in a patient’s near vision improvement.”

One of the factors to consider is ocular rigidity and its impact on presbyopia. “Ocular rigidity is a source of presbyopia in multiple ways,” she said. “It causes scleral rigidity and makes it worse in terms of what happens in the zonules. There is increased lens stiffening.”

A procedure known as laser scleral microporation targets scleral rigidity by “uncross-linking,” potentially helping with biomechanical softening, improving ciliary muscle efficacy to relax the zonules, reshaping the lens during accommodation, and minimizing positive spherical aberration, Dr Yeu explained. She also noted that 10-year data on patients suggest that 3-line improvement in near vision is maintained.

Ophthalmologists have a variety of lenses available for presbyopia correction, including trifocal IOLs, bifocal IOLs, monofocal IOLs, enhanced monofocal IOLs, enhanced trifocal IOLs, and extended depth of focus (EDOF) IOLs. “The enhanced monofocal [IOL] can be used in any patient [in which] you would use a monofocal lens,” Dr Yeu said. However, Dr Yeu also noted that enhanced monofocals are not classified as EDOF lenses and that presbyopia correction options are being tailored to specific corneal issues, such as post radial keratotomy, post LASIK, keratoconus, and iris trauma.

In selecting IOLs for patients, clinicians must consider a patient’s lifestyle, hobbies, and activities. It is also important to evaluate a patient’s tolerance of visual disturbances, such as halos and rings around lights at night, Dr Yeu explained.

Other exciting options on the horizon for presbyopia correction include modular accommodating lenses, Dr Yeu noted, adding that vision gains in studies are impressive. “[Lenses] are very close to entering phase 3 studies,” Dr Yeu said. “[Lenses] are fluid filled and would provide accommodation. The base is first inserted, followed by the insertion of the optic. Because it is completely filling the bag, no [posterior capsule opacification] has been seen in any of these patients, which is very important.”

The hurdle in integrating this IOL into clinical practice may have to do with concerns about insertion of the base of the IOL. However, Dr Yeu said that advances in presbyopia correction and what is in pipeline are certainly encouraging. “It is exciting to see where we were 5 to 7 years ago vs where we will be 10 years from now, with respect to various options and what we will offer in presbyopia correction,” she said.

Yeu is a consultant for and does research with Tarsus Pharmaceuticals and Alcon.

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Thanks to recent innovation, ophthalmologists have several options at their disposal for the treatment of presbyopia.

Medical and surgical treatments emerge for presbyopia

An adaptive optics (AO) retinal camera has been used to measure photoreceptors preoperatively and following macular hole (MH) surgery to accurately assess any changes in cone density, according to research presented by Dr Paola L. Oquendo at the 2022 Canadian Ophthalmological Society Annual Meeting and Exhibition held in Halifax, Nova Scotia, Canada.

“We hypothesised that cone density will change following macular hole closure,” said Dr Oquendo, a vitreoretinal clinical research fellow at St Michael’s Hospital Toronto and the Department of Ophthalmology and Vision Sciences at the University of Toronto in Canada. “This is because it is likely that the temporal retina stretches to close the macula hole. This could possibly result in a reduction of cone density temporally.”

Discussing MH and photoreceptor changes using high-resolution imaging with adaptive optics, Dr Oquendo described the results of a small study that used an AO retinal camera (rtx1, Imagine Eyes) and spectral-domain optical coherence tomography (SD-OCT) to evaluate the photoreceptors in patients with various morphologies of MH and the changes following surgical closure.

The study included individuals presenting to the Kensington Vision and Research Centre in Toronto with idiopathic MH needing pars plana vitrectomy and membrane peeling. Patients underwent extensive imaging before surgery and at 3 months postoperatively, according to Dr Oquendo.

In terms of results with eight patients (eight eyes) with idiopathic MH, cone density before surgery was 11,793.92 mm3,and at 3 months postoperatively it was 12,181.6 mm3. In addition, average preoperative spacing was 24.2%, and postoperatively it was 23.1%.

Preoperative regularity was 85.8%, and postoperative regularity was 85.1%. Five patients had stage 2 MHs, three had stage 3 and one had stage 4. All had successful closure of their MHs.

“There was no statistical difference in cone density, regularity or dispersion when comparing pre- and postoperatively,” Dr Oquendo explained. “The sample size was relatively small, but the study demonstrated that AO (rtx1 retinal camera) may be a useful method of assessing integrity of the cone mosaic following macular hole repair.”

Dr Oquendo noted that the sample size in this study was small. “We would like to continue recruiting patients to enlarge the sample size and get more meaningful data,” she said. “This initial study was a pilot project to assess the cone mosaic before and after surgery, and larger studies will be useful to assess AO imaging biomarkers with variations in surgical technique for macular hole closure.”

Dr Oquendo explained that the significance of the study is that it looked at the effect on cone mosaic following MH surgery. “It is well reported that there is a shift of the retina after surgical repair of the macular hole,” she said. “However, there are very few studies that describe the cone mosaic after surgical repair of MHs.”

Moreover, she pointed out, this is the first study describing the change in cone mosaic from baseline. “It is important to know the integrity and changes in the cone mosaic in macular hole to better understand the mechanism of closure and identify imaging biomarkers that may be associated with better functional outcomes,” Dr Oquendo said. “Eventually this could lead to improved surgical techniques.”

One of the limitations of the technology is that its use can be time-intensive for clinicians, explained Dr Rajeev H. Muni. The senior author on the study, Dr Muni is a vitreoretinal surgeon at St Michael’s Hospital, Toronto and Kensington Eye Institute, and vice-chairman of clinical research in the Department of Ophthalmology and Vision Sciences at the University of Toronto, Canada.

“There is some training that is required before learning how to efficiently obtain images,” Dr Muni explained. “However, if the patient moves or does not fixate on the target, it can be difficult to acquire images. As a result, in some cases the image acquisition process is time-consuming. Furthermore, depending on the objective, performing imaging in many quadrants and several eccentricities will take more time.”

Dr Muni noted that the AO retinal camera will probably have an adjunctive imaging role to SD-OCT. “Both machines are different, and this is not a replacement for SD-OCT,” he added. “This imaging device provides a very high-resolution image of the cone mosaic, and I think it will be complementary to SD-OCT. Currently, I believe it has a lot of potential in research, as we discover novel imaging biomarkers that are associated with functional outcomes in various diseases.”

Dr Muni noted that the AO retinal camera has been used for conditions other than MH. “There are several applications in both medical and surgical retina, and these will keep expanding as we learn more and get more experience,” he pointed out.

“There has been a lot of research already in diabetic retinopathy and hereditary eye disease. It is also very good for measuring the vessel wall thickness in various vascular conditions. The best images can be acquired in younger phakic patients with no media opacity and a good tear film with a good ability to fixate.”

Dr Oquendo had no relevant financial disclosures related to this content.

Dr Muni is a consultant for Alcon, Bausch + Lomb, Bayer, Novartis and Roche. He has received grants/research funding from Bayer, Novartis and Roche.

A small study demonstrates that high-resolution imaging with adaptive optics may be a useful method of assessing integrity of the cone mosaic following macular hole repair.

Retinal camera unlocks back-of-the-eye secrets

Genetic testing is key to confirm an ocular genetics disorder and direct patients in the paediatric setting to appropriate resources, according to Dr Ajoy Vincent, medical director of the visual electrophysiology unit at The Hospital for Sick Children, Toronto and an associate professor of ophthalmology at the University of Toronto in Canada.

During his presentation at the 32nd Annual Jack Crawford Day, an annual paediatric ophthalmology update held virtually in April 2022 by the University of Toronto and The Hospital for Sick Children, Dr Vincent discussed when the decision should be made to refer paediatric cases to an ocular genetics clinic. He underlined that a prompt diagnosis will result in appropriate management and disease prognostication, and that it is important that the clinician has a high index of suspicion when seeing paediatric patients who have various visual challenges.

Dr Vincent outlined the general workflow in ocular genetics. This starts with initial triage of a suspected genetic disorder, with cases directed to a specific ocular genetics clinic or a subspecialty clinic such as cornea, glaucoma, anterior segment, neuro-ophthalmology or oculoplastics.

All cases typically undergo multimodal ophthalmic imaging and/or electrodiagnostic testing, he added. After this, a provisional diagnosis is reached and genetic testing is offered to the family, as well as counselling and other support services.

Dr Vincent noted that there are numerous symptoms or clinical scenarios in children that may indicate an underlying genetic condition. For example, when a baby exhibits poor visual behaviour with or without wandering eye movement, common causes can include bilateral cataracts, cortical visual impairment, developmental eye defects or inherited retinal dystrophy.

Hence, clinicians need to note any details of change in visual behaviour, family history of retinal dystrophy and the child’s perinatal history to differentiate between the various causes. “All pertinent information should be included in the referral,” Dr Vincent stated.

Dr Vincent went on to emphasise, “Some cases require urgent care whereas others may involve a slower referral pattern.” One example of a symptom that may suggest a need for immediate care is nystagmus that presents in a baby. He explained that this condition can be attributed to several factors such as bilateral media opacity, bilateral retinal disease, bilateral optic nerve abnormality and albinism; he noted that retinal dystrophies, metabolic disorders and vestibular disorders can also be responsible for nystagmus.

“One thing that should be evaluated is the direction of the nystagmus, whether it is horizontal, vertical or torsional,” Dr Vincent said. “It should also be evaluated to determine if it is bilateral or unilateral, symmetrical or asymmetrical, conjugate or dysconjugate, and the age of onset.”

If a child has vertical nystagmus or torsional nystagmus that is asymmetrical, dysconjugate in nature, and appears in the first 6 months of life, the nystagmus can be suggestive of a tumour, Dr Vincent said. “This can be indicative of an optic pathway glioma. It is important to state this in the referral so that the patient can be immediately seen by the neuro-ophthalmology team at the hospital. Relevant history can help us to better help these children.”

Another presenting symptom that can include a genetic component is night blindness or nyctalopia. “Commonly, this can be an indication for inherited retinal dystrophy,” Dr Vincent said, citing retinitis pigmentosa as an example.

He noted that another of the reasons for night blindness may be vitamin A deficiency. “These days, sometimes we see children who have vitamin A deficiency because they have picky eating habits,” he said. “Some of these patients have autistic spectrum disorder, which can influence eating behaviours.”

In these cases, Dr Vincent noted it can be important for the ophthalmologist to ask about a patient’s history, family history and any symptoms of constriction of visual field. “Ask if the child bumps into objects, or ask about any general health-related questions regarding hearing, kidney health, heart health or digital anomalies, as this may help to diagnose complex (syndromic) disorders,” he said. “Include any relevant information in the referral.”

If a child’s visual acuity cannot be fully corrected for their age with glasses, if the fundus exam is normal and if the child does not have amblyopia, then a retinal dystrophy is a likely diagnosis and requires a referral, Dr Vincent said. If the fundus exam is abnormal, it could either be because of macular dystrophy or be due to an optic neuropathy of various aetiologies.

Progressive distance vision loss over a short period of time is another clinical scenario that requires a referral, Dr Vincent noted. “You have to determine if it is sudden onset over a few days or over a period of a few months,” he said. “If it is a few days, it is likely an optic neuropathy or neuritis or acquired maculopathy. If it has been over a period of a few months, it could be the beginning of macular dystrophy or Batten disease, with the latter being a neurodegenerative condition.”

Genetic testing can be useful because it can provide an accurate diagnosis and prognosis, Dr Vincent emphasised, pointing to retinitis pigmentosa as a case in point. “There are over 100 genes that can cause retinitis pigmentosa,” he said.

He pointed out that not all cases of retinitis pigmentosa have the same disease progression or disease pathway. “It can be specific for various genes, so it is very important that we do genetic testing and confirm the diagnosis. In this way, we can [give patients an] accurate or a more reasonably accurate prognosis.”

Dr Vincent has no financial disclosures related to this content.

Clinicians need to investigate patients’ history, family history, visual behaviours and general health in order to promptly and accurately refer paediatric cases to ocular genetics clinics.

Knowing when to refer young patients to ocular genetics programmes

Minimally invasive strabismus surgery in adults is quicker and safer than the traditional method, according to Dr Yi Ning Strube, an associate professor and director of paediatric ophthalmology and adult strabismus at Queen’s University in Kingston, Ontario, Canada.

During her presentation at the 32nd Annual Jack Crawford Day, an annual paediatric ophthalmology update held virtually in April 2022 by the University of Toronto and The Hospital for Sick Children in Toronto, Canada, Dr Strube described the advantages of the minimally invasive approach.

“Minimally invasive strabismus surgery is less risky to the patient, and less painful, with faster recovery compared to our traditional strabismus procedures,” she explained. “It is easier and faster for the surgeon and therefore less stressful.”

One of the minimally invasive strabismus surgical techniques is the central tenotomy, which can be performed with the patient fully awake as an in-clinic procedure. “This procedure can correct small vertical tropias of 1 to 2 [prism dioptre],” Dr Strube explained. “It is a simple and quick procedure that you can do under topical anaesthesia.”

Dr Strube discussed a case in which a central tenotomy was used on a surgeon who had a retinal detachment that was repaired but had residual vertical diplopia and did not want to wear prism glasses. The procedure provides a surgical alternative to prism spectacles; it corrects very small deviations previously not amenable to surgical correction, as standard rectus muscle recessions correct much larger deviations.

 published in 2009 of 15 consecutive cases by Dr Kenneth Wright, a paediatric ophthalmologist and founder of Wright Center for Pediatric Ophthalmology and Adult Stabismus in Los Angeles, California, United States, looked at the success of the central tenotomy procedure he developed to correct diplopia associated with small-angle strabismus.

Patients in the series were aged 35 –86 years, and 11 of 15 were 60 years and older. All 15 patients had binocular diplopia, and five of 15 were using prism glasses prior to surgery. Dr Wright reported successful treatment of hypertropia with the central tenotomy, but not for esotropia; the procedure is therefore not recommended for patients with esotropia as they often have a much larger underlying esophoria.

Dr Strube outlined a few important steps to keep in mind when performing the central tenotomy. Firstly, topical anaesthetic is applied to the eye, followed by a drop of phenylephrine 2.5% to blanch conjunctiva; this allows for improved visualisation of the anterior ciliary vessels, which should be avoided. Additionally, a drop of antibiotic should be applied.

A 0.50- or 0.75-toothed forceps is used to grasp the central tendon of the rectus muscle through the intact conjunctiva. “You want to move the eye and be sure you haven’t just grasped the superficial conjunctiva,” Dr Strube said.

“Make sure you are using blunt Westcott scissors and be very careful not to go too deep. You are going to hear a click when you cut through the tendon.” The central tendon is cut between the forceps and sclera through the intact conjunctiva, with the central third of the tendon more relaxed, and the two muscle poles left intact, maintaining the normally broad insertion.

“The nice thing is this is repeatable, either at the time of surgery, or if the diplopia should recur,” Dr Strube said. “The patient will tell you if they have improved or not at the time of the procedure if you are performing awake in the office. A procedure like this opens up treatment options for patients without using valuable OR time.”

Another minimally invasive strabismus procedure is the central plication, a rectus muscle tightening procedure. Technically, the procedure involves a modified swan incision over the muscle, Dr Strube noted, citing another study by Dr Wright and Dr Rebecca S. Leenheer, a pediatric ophthalmologist with Family Eye Care and Children’s Eye Center of New Mexico in Albuquerque, New Mexico.

Results of the retrospective study, which categorised patients by hyperdeviations, esodeviations and exodeviations, showed that all patients experienced a decrease in strabismus following the plication procedure. In addition, diplopia was noted in 50% of the adults preoperatively and none postoperatively.

“It corrects more than the tenotomy, about 6 to 8 prism dioptres per muscle,” Dr Strube explained. “Again, this is a procedure you can do under topical anaesthesia. It is a vessel-sparing procedure, and it can be reversed if needed by cutting the sutures in the first day or two. It is really great for small angle deviations. It is hard to do a recession or resection to correct such a small amount (of deviation).”

“On average, you get about 5 to 6 prism [dioptres] per muscle,” Dr Strube noted. “You can correct about 8 prism dioptres if you are performing against a previously recessed antagonist muscle.”

Dr Strube noted that it is important to remember that pulling on the muscle is very painful for the patient and that with minimally invasive strabismus surgery, topical anaesthetic will not completely address that problem. Careful tissue handling and proper technique can avoid pain, for example, by using a traction suture to manipulate the eye rather than pulling on the muscle.

“The central plication is an invaluable technique that is great for patients [post-LASIK and post-cataract surgery] with small-angle strabismus who are keen to be out of glasses, and [it is] an additional technique for complex strabismus patients,” Dr Strube concluded. “Both the central plication and central tenotomy procedures eliminate the need for adjustable strabismus surgery, as these simple techniques can be performed as needed as a touch-up surgery to correct residual small angle deviations.”

Dr Strube has no relevant disclosures related to this content.

1. Wright KW. Mini-tenotomy procedure to correct diplopia associated with small-angle strabismus.

2. Leenheer RS, Wright KW. Mini-plication to treat small-angle strabismus: a minimally invasive procedure. 

Central tenotomy and central plication are just two options that can correct very small deviations previously not amenable to surgical treatment.

Author | Louise Gagnon

Articles

Retinal camera unlocks back-of-the-eye secrets

Knowing when to refer young patients to ocular genetics programmes

Pearls for minimally invasive strabismus surgery

Medical and surgical treatments emerge for presbyopia