From the dangers of eating lamb mince to the mysteries of the media, this year’s Ophthalmology Updates! presented mind-bending, bitesized updates in eye health for ophthalmologists, optometrists, and orthoptists alike.
Now in its sixth year, Ophthalmology Updates! has become a permanent fixture on the calendar for eye care professionals craving the latest and greatest information across all ophthalmology subspecialties.
Whereas Ophthalmology Updates! was held in conjunction with RANZCO NSW’s annual conference in 2022 (a protective measure as we emerged from COVID), this year’s event was independently run with founder and retinal surgeon Professor Adrian Fung once more at the helm.
With speakers presenting multiple 10-minute lectures – some directed by the convener, others out of pure interest – it would be impossible to cover all topics here. Instead, we present a select few.
SUNSHINE AND SQUAMOUS CELL CARCINOMA
The simple observation of a squamous cell carcinoma (SCC) on an eyelid – and a subsequent course of action – may save a life.
Professor Dinesh Selva informed the audience that reddish, scaly plaque on the eyelid signals actinic keratosis, with potential to turn into a squamous cell carcinoma (SCC) in situ. In the peri-orbital region, actinic keratosis presents as flat or thickened, and sometimes elevated papules. When biopsied, it may be mildly, moderately or severely dysplastic.
While the risk of an actinic keratosis becoming an SCC is pretty low – 0.1% per lesion per year, with multiple lesions the risks rise. Risks also increase with lesions of larger dimensions (more than 1cm in diameter) and other factors such as being immune compromised.
A patient’s risk factors will dictate the treatment to be used, however the key is to liaise with their dermatologist. Being so close to the eye, treatment is a difficult decision.
Efudex (5-Flurouracil) and cryotherapy are generally avoided near the lid margin. Aldara (Imiquimod), despite being contraindicated in the periocular region, may be used in selected cases. Prof Selva recommends excision in selected patients with very high-risk lesions.
SCC in situ must be more aggressively managed as there is a 5% cumulative risk of it becoming invasive. The approach is to excise it with frozen section margin control if possible. Topical treatments including creams and topical chemotherapy and other destructive treatments, such as cryotherapy, photodynamic therapy, and radiotherapy can be challenging due to its position on the eyelid.
Prof Selva also spoke about keratoacanthoma, a common, rapidly growing, crateriform, locally destructive skin tumour that can be indistinguishable from invasive SCCs. A significant percentage of lesions presenting in this manner (around 20%) will turn out to be truly malignant invasive SCCs. With keratoacanthoma, you can’t predict the size it will get, whether it will regress, or whether it will cause scarring, distortion or disfigurement of the eyelid. Hence, excision is recommended.
Finally, delegates were advised to be aware of the risk of histological perineural invasion (PNI) of an SCC, and perineural spread. SCC has a propensity to spread via the nerves and can lead to sensory and motor symptoms such as numbness and muscle weakness.
Perineural spread “can also be quite indolent – a patient with an unexplained facial palsy that’s gone on for a year, their MRI scan is normal”. These patients should be monitored with high suspicion. Over time the SCC can spread from sensory to motor nerves. Early detection is important “as it is treatable in the early stages before it reaches the brain stem”. “There are reasonable outcomes with surgery and radiotherapy. It’s very important that we think about it and pick it up,” Prof Selva said.
ABOUT LAMB MINCE
Who would have thought that one in every 150 Australian Boomers has a toxoplasmic scar caused by a parasite found in meat? This surprise finding came from the recent Busselton Healthy Ageing Study and was presented at Ophthalmology Updates! by Professor Justine Smith.1
Described as ‘the world’s most effective parasite’, Toxoplasma gondii infects a third to a half of all of us. However fortunately, congenital infections are very rare. While known to be carried by cat faeces, Prof Smith informed the audience of European data suggesting that many infections come from eating meat that is raw or undercooked.
Any meat can be contaminated with Toxoplasma. Researchers testing for Toxoplasma in lamb mince detected the parasite’s DNA, conservatively in 43% of purchases and more liberally in 68% of purchases.1
Prof Smith recommended cooking your meat to medium and if you like to eat it rare, freezing it overnight before you prepare it to kill the parasite.
Mechanisms of Action
Prof Smith leads a laboratory research team that has spent many years studying the mechanisms behind ocular toxoplasmosis.
She said that after becoming infected with Toxoplasma, people are more likely to develop disease in the retina than in other parts of the body for several reasons.
The retinal endothelial cells that line the retinal blood vessels are extra susceptible to infection with Toxoplasma, and the parasite can also move across the retinal endothelium as a free parasite or in highly motile white blood cells.
Once it finds its way into the retina, Toxoplasma can wriggle its way through; it likes to infect the glial cells and in doing so, gains access to all parts of the retina. Finally, it heads down to infect the retinal pigment epithelium, causing these cells to proliferate, making them more susceptible to infection with the parasite. Additionally, the infected retinal pigment epithelium releases soluble factors that control the behaviour of white blood cells in the eye.
“So, if you become infected with Toxoplasma, it’s most likely to cause disease in your retina, causing a characteristic picture that is often diagnosed clinically,” she said.
The Disease
Primary ocular toxoplasmosis is more common in men than women, however women are more likely to have more than one lesion, and the lesions in women are more likely to occur at the posterior pole. There are no differences in the rate of reactivation across genders, the numbers and types of complications, or visual outcomes.
Eyes with ocular toxoplasmosis have many different features on optical coherence tomography (OCT) imaging, and one of these has been linked with blindness.
Most clinicians diagnose typical ocular toxoplasmosis on its clinical appearance or the clinical appearance plus serology testing, the latter being most useful when negative because the parasite infection is so common.
Management
Two thirds of uveitis specialists treat all patients while about a third treat selected patients depending on considerations like where the lesion is, whether it is affecting the vision, and the presence of complications. Patients who are immune compromised and patients having their first episode should always be treated.
Treatment is usually with antimicrobials, in the first instance systemically. Many clinicians use adjunctive corticosteroids orally and sometimes topically, but not by injection, which could exacerbate the infection.
Intravitreal therapy is also used, and several injections may be necessary to get the disease under control.
Prophylactic antibiotics are used as a preventative if there is concern about recurrences, and in patients who are immune compromised, since the infection is never eradicated.
Treatment of pregnant women poses a special and complex situation and should be undertaken in collaboration with the obstetrician.
FUTURE TREATMENTS FOR AGERELATED MACULAR DEGENERATION
Professor Robyn Guymer spoke about agerelated macular degeneration (AMD) and emerging treatments. Via a poll, delegates agreed that although anti-VEGFs have had a significant impact on neovascular AMDoutcomes, the most significant problems were that patients still lose vision in the medium-to-long term, and there are not enough durable treatments.
Outcomes from the Fight Retinal Blindness! Registry show that even with optimal dosing frequencies, for the remaining lifetime of 11 years, an estimated 12% of a sample 3,192 patients retained driving vision and 15% retained reading vision in at least one eye.
The dream panacea for clinicians and patients alike may be for a once-off gene therapy. Three routes of administration are being explored for ocular gene therapy – subretinal, suprachoroidal, and intravitreal.
A subretinal approach results in minimal exposure to the viral implant so it is less likely to cause an immune response; the suprachoroidal route (which may be able to be performed in office) is less likely to get an immune response; however intravitreal delivery, the easiest delivery, is more likely to give an immune response, which means patients would need to take a systemic suppressant. Research continues.
In the meantime, researchers are looking at longer lasting anti-VEGF treatments. Roche has completed its trials for an implantable reservoir-based low release anti-VEGF platform that sits in the sclera and delivers a ranibizumab-like drug. After the initial fill, it would then be re-filled in office using a special needle.
Prof Guymer reported that Phase 2/3 trials with this implant had demonstrated similar gains to regular dosing of ranibizumab. At the highest concentration, 80% of patients were able to go to six months or longer until requiring their first refill.
While the United States Food and Drug Administration approved the implant for adults who had previously responded to two or more anti-VEGF injections, it has currently been withdrawn from the market due to septum dislodgement on refill. While extending treatment intervals is a priority, Prof Guymer said she is most interested in any treatment that might reduce the vision loss from atrophy or fibrosis, the cause of medium-term vision loss in those being treated with anti-VEGF. She was also interested to understand why the real-world data often fell short of clinical trial outcomes. She wanted to understand how clinicians were interpreting OCT signs of atrophy and their different treatment regimens, for example how people were tolerating stable subretinal fluid.
She believes faricimab, with its dual action, might offer the ability to reduce atrophy and fibrosis given results from animal studies reporting less inflammation when the anti-ang-2 component was added to antiVEGF, which may overcome the problem of subretinal fluid. Combining an antiVEGF action and an ang-2 action provides greater vessel stability and may reduce inflammation cell death, she said. It may also increase durability.
Mouse studies showed that at week one, and out to two months, the dual inhibition reduced inflammation, vascular leakage, and fibrosis.
“So, my particular interest is in what’s going to happen down the track when using this drug? Preclinical models show we may be able to reduce fibrosis and atrophy… it’s a wait and see,” Prof Guymer said.
She currently uses faricimab as a first-line treatment for all patients, in the hope it offers more to address the current unmet need of vision loss due to atrophy and fibrosis, not due to lack of efficacy of current anti-VEGF drugs.
TO TRUST OR NOT TO TRUST
Ophthalmology Updates! is known for inviting a keynote speaker from outside the sector to share their perspectives on life and this year it was Walkley Award-winning health journalist and founder of the Coronacast podcast, Dr Norman Swan.
Dr Swan, who trained in medicine and specialised in paediatric healthcare before entering the world of journalism, spoke about the influence of the media – good and bad – on recent debates of national interest, specifically The Voice referendum and the coronavirus pandemic.
He drew attention to a trend away from evidence-based reporting in favour of fearmongering with negative stories, which he illustrated with real life examples.
Additionally, he spoke about the future of the media, which will see traditional channels dismantled in favour of more digital ondemand options. This will make it increasingly difficult for the public to discern trustworthy evidence-based news from fake news.
Dr Swan left us to question: who do we trust, who do we believe?
Ophthalmology Updates! returns with more disruptive discussion in August 2024.
Reference
- Dawson, A.C., Ashander, L.M., Appukuttan, B., et al., Lamb as a potential source of Toxoplasma gondii infection for Australians. Epidemiology 11 December 2019 doi. org/10.1111/1753-6405.12955.
