 without eyedrops has long been a goal for ophthalmologists. However, whilst it may be possible one day, it is not yet a reality and anti-glaucoma drops currently remain the first-line choice for many ophthalmologists.

Numerous surgical procedures and minimally invasive devices are also available to lower intraocular pressure (IOP). Some have been around for a long time, but within the past few years, numerous devices have entered the market with unknown long-term results and there are more still in the pipeline.

Eliminating the potential land mines in glaucoma surgery

Despite great progress in the field, the question remains as to which glaucoma treatment(s) can achieve and maintain the desired IOP level and prevent progression, according to Dr Janet B. Serle, professor emeritus of ophthalmology, Icahn School of Medicine at Mount Sinai, New York, United States.

Clinicians can adhere to the general guidelines that have been established for target IOPs for different glaucoma stages, however, how well they work for individual patients remains to be seen. “For each patient, it is important to assess the risk parameters in addition to the stage of the disease,” Dr Serle said. “In some patients, we can hopefully get ahead of progression by treating the glaucoma aggressively, and in other patients we may be able to step back, accept higher target IOPs and carefully assess the most appropriate therapies.”

Many large clinical trials have evaluated specific procedures over different follow-up periods of time. The trials have generated widely varying outcomes regarding medication use and wide-ranging IOP results postoperatively. These range from no medications needed in 78% of patients followed for 3 years after selective laser trabeculoplasty (SLT)

 to studies of minimally invasive glaucoma surgeries (MIGS) and gonioscopy-assisted transluminal trabeculotomy that resulted in a wide range of medications needed postoperatively.

Dr Serle suggested that surgeons look outside the treatment box, rethink the current order by which they select treatment and determine if they should adjust that order. For example, should surgeons consider an SLT, an earlier SLT or a MIGS procedure, if appropriate, or should patients be treated more aggressively earlier in the disease process, especially in the case of young patients with potentially longer life spans? Another challenge, she pointed out, is identifying and diagnosing patients with early disease.

“I do not think it is time to abandon the traditional more invasive procedures, particularly in advanced disease, because these more consistently result in lower IOPs,” she commented.

Currently, however, although there are numerous non-medical options that are available for glaucoma management, physicians cannot now achieve successful IOP control in all patients without relying on medical therapy.

Using pivotal study data to guide glaucoma patient management decisions

Dr Serle emphasised that to manage and control glaucoma without eyedrops, there must be a more “robust” way to identify patients with glaucoma, especially those with early disease. Acceptance and incorporation of other, newer treatment options by patients and physicians should occur.

If intervention is successful, the progression curve may change, she said, and she noted the importance of demonstrating that surgical devices and procedures achieve satisfactory target IOPs for long durations during a patient’s life. The current devices meet the target IOPs in some patients, but the long-term results are unknown.

Dr Serle said that it should be a goal to reduce the medication burden as much as possible. “Physicians can think about how they select treatment,” she said. “For patients with early-stage glaucoma, consider options other than medications.”

Precision management to revolutionise glaucoma diagnosis and treatment

She added: “In moderate and late-stage disease, treatment with laser and/or MIGS and/or traditional surgery may reduce or eliminate the need for medications in some patients. For late-stage disease, more invasive surgeries may be more successful at achieving the required IOP with fewer or no medications.”

Gazzard G, Konstantakopoulou E, Garway-Heath D, et al. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. 

This article is adapted from Dr Serle’s presentation at the American Glaucoma Society’s 2021 virtual annual meeting. Dr Serle is a consultant to Aerie Pharmaceuticals, Allergan, Bausch + Lomb and Qlaris.

Articles

Ophthalmologists should consider numerous options for treating individual glaucoma patients, including non-medical interventions.

Dropless glaucoma treatment: An elusive path to ease burden

When we come to the management of diabetic macular edema, the treatment options are much more diverse. Dr. Korobelnik, could you focus a little bit on anti-VEGF [vascular endothelial growth factor] therapy, steroids, implants, and combination therapy? Perhaps you could also address your opinion concerning micropulse laser treatment? Possibly as a monotherapy and in combination setting?

 I truly agree with that. For DME [diabetic macular edema], we have more options than for wet AMD [age-related macular degeneration]. Of course, we use the same VEGF inhibitors as we used in AMD. As Tunde said, we use them based on local regulation and how the drugs are covered. However, for DME we can use steroids; maybe not as a first-line treatment, it can be in some cases, but it’s definitely something that is to be considered in DME patients. As you said, we have laser treatment. Micropulse is something that is interesting, but we miss some truly demonstrative studies to be sure that it is effective. Now we also have targeted photocoagulation in [INAUDIBLE] that has been abandoned since VEGF inhibitors came. It is now able to be done precisely based on the fundus photo of the fluorescein or late ICG [indocyanine green angiography]. For DME, we definitely have the choice. Each one has to consider whether they want to do first. However, most often the first choice is VEGF inhibitors. Many patients are responding. However, depending on the patients’ response and the capacity of the patients being able to attend appointments, we may select other options. Of course, do not forget to look for, check, and control glycemia to control blood pressure. Those systemic parameters are extremely important for DME. We see some patients when their blood pressure is well controlled, their glycemia is well controlled, and things get much better.

 Can I add something to that before you ask your next question? There might be some listeners who are from countries where anti-VEGF agents are not widely available, or people need to buy them and they can’t afford them. You always should do a clinical examination and try to figure out if laser, if you have, might be useful. Some patients will be helped by laser treatment initially. If that is the case, then it’s important it is done. Additionally, laser treatment has been used in a lot of anti-VEGF and steroid trials. Sometimes it is possible to treat; to give an additional laser treatment and make sure those patients who might not be able to afford more treatment injections are able to get some benefit from that treatment as well.

 I fully agree Tunde. One very important thing to consider in diabetic patients is not to focus only on the macula but look at the periphery. You can have diabetic retinopathy, lung perfusion, and, in some cases, proliferation of new vessels. We do see from time to time in some patients that are being treated for DME, and they have proliferative disease that was underdiagnosed. You must evaluate the periphery in those patients.

 This is becoming a real issue during COVID-19 when people did not get their injections. Suddenly, they come back with bad diabetic eye disease, with rubeotic glaucoma, because it was the injection that kept it at bay. Good examination and laser treatment would be very helpful for a lot of patients still.

Anyhow, our focus for today is diabetic macular edema. I fully agree that we must look for those people as well, and we must look for systemic control and retinal periphery.

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A discussion regarding the roles of various treatments available for diabetic macular edema and considerations for selecting and sequencing therapy.

Diabetic Macular Edema: Treatment Overview

I would like to move forward to the treatment of those diseases. I would like to review the current treatment landscape firstly for the management of AMD [age-related macular degeneration]. Dr. Peto, could you say a few words on patient factors which influence our treatment strategy when we consider [a] specific agent?

 Several countries have different legal allowances as to which drug you can use. It is very important that people stay within their legal framework and what has been registered in their own countries. In several countries, we have 2 or 3 drugs available for treating age-related macular degeneration. Which one you start with tends to be somewhere between personal preference or what your system allows you to do. We always need to think about the vision, potential outcomes, and potential comorbidities. If the patient has just had a stroke or heart attack, we might not be able to treat them with the agent of choice. We also need to think about how many times the patient would be able to come back to clinic. All of these need to be discussed right at the beginning, because we are likely to see the patient very often in the first year of treatment at least. We must tell them that we do not really fully understand as to who will respond very well to treatment and who might have slightly less treatment frequency in the second and third year, while others may require very frequent injections for the duration of the disease. We might have to also tell them that their vision might be going up and down depending on if they might have a hemorrhage. It is important that we warn them about all of the complications of the disease as well.

An overview of the current treatment landscape for age-related macular degeneration and factors that impact treatment selection.

Age-Related Macular Degeneration: Treatment Overview

Not all randomised controlled trials (RCTs) are equal: depending on the scientific question asked and the robustness of methodology, some can substantially affect clinical practice and are therefore considered landmark studies. Although it is now well established that IOP reduction is the cornerstone in the management of 

 it was not until the late 1990s that the evidence to support this notion became available.

A number of landmark RCTs published in the late 1990s and early 2000s provided solid evidence that the lowering of IOP reduces the risk of progression of open-angle glaucoma (OAG)

 and the risk of conversion of ocular hypertension to OAG.

 Two additional landmark RCTs independently identified the same risk factors for the conversion of ocular hypertension to OAG.

 These data enabled the development of a risk prediction equation with predictive utility (risk calculator).

Although these early landmark studies were hugely important for the management of ocular hypertension and OAG, questions remained unanswered regarding the medical and surgical management of glaucoma. Some of these questions have been answered by more recent landmark RCTs, which I will discuss here.

Whereas aqueous shunts were already commonly used for the management of complex/refractory glaucoma and were starting to become popular as an alternative to trabeculectomy in those at high risk of filtration failure, it remained unknown which was the best approach for patients with prior ocular surgery. The Tube Versus Trabeculectomy(TVT)

 study was designed to investigate the safety and efficacy of tube shunt surgery versus trabeculectomy with mitomycin C (MMC) in eyes with prior cataract and/or filtration surgery.

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The study enrolled 212 patients who had had prior cataract and/or failed filtration surgery and uncontrolled glaucoma on the maximum number of medications. Outcome measures were: IOP; visual acuity; visual field; surgical complications; glaucoma medications; and treatment failure. The follow-up period was 5 years.

The cumulative probability of failure was higher for trabeculectomy versus tube shunt surgery. No difference in mean IOP was observed, but IOP control in the first 2 years was better with trabeculectomy. Early complications were more frequent with trabeculectomy but there was no difference in late postoperative complications.

There was no significant difference between groups in the number of medications needed, although the trabeculectomy group required fewer in the first 2 years. Thus, theTVT study provided evidence that both tube surgery and trabeculectomy with MMC are appropriate in those with previous cataract and/or failed filtration surgery.

However, the study’s results need to be interpreted with caution because the subgroup of patients with previous failed trabeculectomy may have introduced bias in favour of the tube group. For the same reason, tube surgery may be more appropriate in those with failed filtration surgery. The TVT study challenged the traditional paradigm that tube shunts should be reserved for patients with refractory glaucoma.

The purpose of the Primary Tube Versus Trabeculectomy (PTVT)

 study, which followed on from the TVT study, was to investigate the safety and efficacy of tube shunt surgery versus trabeculectomy with MMC in eyes without prior filtration surgery. The population size was 242; patients had not had prior filtration surgery and had uncontrolled glaucoma on maximum medications.

The outcome measures were rate of surgical failure, mean IOP, complications and reoperation for glaucoma. The follow-up period was 3 years.

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The PTVT showed that both tube shunt surgery and trabeculectomy with MMC are effective in lowering IOP as a primary glaucoma procedure. However, trabeculectomy may be more appropriate if the target IOP is quite low, such as in normal pressure glaucoma.

Given the higher rate of success and the need for fewer medications in the trabeculectomy group, the latter may be more appropriate if a goal of surgery is to minimise the use of glaucoma eyedrops. In vi

ew of the similar rates of reoperation for glaucoma found between the groups, trabeculectomy should probably be the primary procedure of choice in younger patients.

Despite the wealth of data on the efficacy of IOP-lowering treatment in the management of OAG, before 2014 there were no data from placebo-controlled trials to demonstrate efficacy in the preservation of visual function. In addition, although prostaglandins were in common use as first-choice treatment for the management of OAG, there was no published evidence for a protective effect on vision.

The UK Glaucoma Treatment Study (UKGTS) was the first placebo-controlled trial to investigate whether treatment with a topical prostaglandin reduces the frequency of visual field progression in patients with OAG compared with placebo.

A secondary analysis was conducted to explore risk factors for visual field progression.

 In this study, which enrolled 516 newly diagnosed OAG patients, the outcome measure was time to visual field progression and patients were followed up at 2 years.

The UKGTS demonstrated that topical prostaglandins are effective at preserving visual function in OAG, even in those with relatively low baseline IOP. However, two-thirds of patients in the placebo group had no detectable progression within 24 months, so one could consider an observation period before starting treatment in certain patients with OAG. This approach may help identify those who might be suitable for monitoring alone, thus avoiding the unnecessary burden of treatment.

Study examines pairing phacoemulsification with implantation of stents

The study identified bilateral disease, higher IOP and disc haemorrhage as risk factors for visual field progression, and treatment with latanoprost and possibly smoking history as protective factors against visual field progression. The likelihood of lifetime visual impairment is an important factor to consider. With the average life expectancy from the diagnosis of OAG having been estimated at 9–13 years,

 the benefits of treatment need to be balanced against the risk of overdiagnosis

In addition, the UKGTS has shown that, with appropriate study design, it is possible for future RCTs to detect differences in visual function in a much shorter period than the typical 4–5 years used in previous trials. This knowledge is hugely important for novel drug development with consequent cost reduction.

The aforementioned landmark RCTs focused on OAG, which remains the most common type of glaucoma across the world.

 Comparatively little attention was paid to primary angle closure glaucoma (PACG), which accounts for 25% of glaucoma cases worldwide. Though not as common as OAG, PACG tends to progress faster and, therefore, is more likely to lead to blindness.

Since the mid-1970s, laser peripheral iridotomy (LPI) was the treatment of choice in primary angle closure and PACG.

 In more recent years, surgical lens extraction has been advocated as an alternative treatment for the disease; however, its effectiveness had not been investigated in high-quality randomised or non-randomised studies.

Considering the best surgical approach in angle closure patients

The purpose of the Early Lens Extraction for the Treatment of Primary Angle-Closure Glaucoma (EAGLE)18 study was to investigate the efficacy, safety and cost-effectiveness of clear-lens extraction versus LPI combined with medical treatment in patients with newly diagnosed advanced angle-closure disease (primary angle closure and PACG).

In EAGLE, 419 patients aged over 50 who had primary angle closure and IOP ≥30 mmHg or PACG were enrolled; outcome measures were patient-reported health status, IOP and cost-effectiveness and the follow-up period was 3 years. 

This study provided evidence that clear-lens extraction has greater efficacy and is more cost-effective than LPI and should therefore be considered as first-line treatment in patients with advanced angle closure disease.

However, one needs to remember that all study participants in the EAGLE study had IOP ≥30 mmHg. Therefore, these data may not apply to all patients with primary angle closure and PACG.

Although the EAGLE study provided clear direction on the best management option for advanced angle closure disease,

 until recently little was known about whether primary angle closure suspects (PACS; defined as those with ≥6 clock hours of no visible trabecular meshwork on gonioscopy, normal IOP, no peripheral anterior synechiae and no glaucoma)

The purpose of the Zhongshan Angle Closure Prevention(ZAP) trial was to assess the efficacy and safety of prophylactic LPI against PACG in Chinese people who are PACS.

In 889 individuals (identified through community-based screening) who had bilateral PACS, the outcome measures were incident primary angle closure disease (composite endpoint of high IOP, peripheral anterior synechiae or acute angle-closure). Patient follow-up was 7 years.

The ZAP trial showed that prophylactic LPI is of modest benefit in PACS. The risk of these asymptomatic individuals developing primary angle closure over a 6-year period was low, (<1%). Based on the data from the study, one would have to treat 44 PACS to prevent one case of new primary angle closure disease over a 6-year period. Therefore, the ZAP trial data do not support the widespread practice of LPI in PACS.

Prior to a study known as ‘selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma’(LiGHT),

 very few randomised trials had compared the outcomes of medical treatment versus laser trabeculoplasty in OAG and ocular hypertension.

Among these, only the Glaucoma Laser Trial had enrolled previously untreated patients,

 comparing the efficacy and safety of argon laser trabeculoplasty versus timolol maleate 0.5%: all patients received both treatments (randomisation per eye).

Therefore, until recently, there were no high-quality data comparing selective laser trabeculoplasty (SLT) with newer IOP-lowering medications in treatment-naive patients, and no data comparing the effects of these treatment options on quality of life (QoL). The LiGHT trial was designed to compare QoL outcomes, clinical effectiveness and cost-effectiveness of SLT versus medical treatment in treatment-naive patients with ocular hypertension and OAG.

The study enrolled 718 treatment-naive patients with OAG or ocular hypertension. Outcome measures were health-related quality of life (HRQoL) at 3 years, cost and cost-effectiveness, disease-specific HRQoL, and clinical effectiveness and safety. The follow-up period was 3 years.

The LiGHT trial was unable to detect a difference in HRQoL between the treatment groups. However, it provided evidence that SLT is more likely to be cost-effective than medical treatment and provides drop-free IOP control in the majority of patients for at least 3 years.

One of the strengths of the LiGHT trial was that the treatment escalation protocol was robust but, at the same time, pragmatic. Therefore, SLT should be considered as first-line treatment in newly diagnosed patients with ocular hypertension and early-to-moderate OAG. However, this also means that one may have to address patients’ perceptions of the necessity of monitoring visits, in the absence of daily treatment.

Another important clinical implication from the LiGHT trial is that few patients are likely to experience a severe IOP spike post-SLT. This is important for patient reassurance, but also for avoiding unnecessary hospital visits post-treatment.

Dr Founti is a glaucoma specialist and a consultant ophthalmic surgeon at Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom. She is also an honorary senior research associate at the University College London Institute of Ophthalmology. She has no conflict of interest related to the subject matter to report.

. 5th ed. Savona, Italy: Publicomm; 2020.

2. Collaborative Normal-Tension Glaucoma Study Group. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. 

3. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. 

4. The AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. 

5. Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. 

6. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. 

7. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. 

8. Miglior S, Pfeiffer N, Torri V, et al. Predictive factors for open-angle glaucoma among patients with ocular hypertension in the European Glaucoma Prevention Study. 

9. Takwoingi Y, Botello AP, Burr JM, et al. External validation of the OHTS-EGPS model for predicting the 5-year risk of open-angle glaucoma in ocular hypertensives. 

10. Gedde SJ, Schiffman JC, Feuer WJ, et al. Treatment outcomes in the Tube Versus Trabeculectomy (TVT) study after five years of follow-up. 

11. Gedde SJ, Feuer WJ, Lim KS, et al. Treatment outcomes in the primary Tube Versus Trabeculectomy study after 3 years of follow-up. 

12. Vass C, Hirn C, Sycha T, Findl O, et al. Medical interventions for primary open angle glaucoma and ocular hypertension. 

13. Garway-Heath DF, Crabb DP, Bunce C, et al. Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial. 

14. Founti P, Bunce C, Khawaja AP,et al. Risk factors for visual field deterioration in the United Kingdom Glaucoma Treatment study. 

15.Saunders LJ, Russell RA, Kirwan JF, et al. Examining visual field loss in patients in glaucoma clinics during their predicted remaining lifetime. 

16. Founti P, Coleman AL, Wilson MR, et al. Overdiagnosis of open-angle glaucoma in the general population: the Thessaloniki Eye Study. 

17. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. 

18. Azuara-Blanco A, Burr J, Ramsay C, et al. Effectiveness of early lens extraction for the treatment of primary angle-closure glaucoma (EAGLE): a randomised controlled trial. 

19. Prum BE Jr, Herndon LW Jr, Moroi SE, et al. Primary angle closure preferred practice pattern(®) guidelines. 

20. Robin AL, Pollack IP. Argon laser peripheral iridotomies in the treatment of primary angle closure glaucoma. Long-term follow-up. 

21. Friedman DS, Vedula SS. Lens extraction for chronic angle-closure glaucoma. 

22. Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and classification of glaucoma in prevalence surveys. 

23. He M, Jiang Y, Huang S, et al. Laser peripheral iridotomy for the prevention of angle closure: a single-centre, randomised controlled trial. 

24. Gazzard G, Konstantakopoulou E, Garway-Heath D, et al. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. 

25. The Glaucoma Laser Trial Research Group. The Glaucoma Laser Trial (GLT). 2. Results of argon laser trabeculoplasty versus topical medicines. The Glaucoma Laser Trial Research Group. 

26. Nagar M, Ogunyomade A, O-Brart DP, et al. A randomised, prospective study comparing selective laser trabeculoplasty with latanoprost for the control of intraocular pressure in ocular hypertension and open angle glaucoma. 

27. Katz LJ, Steinmann WC, Kabir A, et al. Selective laser trabeculoplasty versus medical therapy as initial treatment of glaucoma: a prospective, randomized trial. 

Landmark randomised controlled trials have advanced the understanding and treatment of glaucoma.

The impact of landmark studies on clinical practice in glaucoma

In a strategic move by the company to align their name with their future, BELKIN Laser will now be known as 

. The Israel-based medical device company will continue to supply fast, accessible 

 laser treatment as well as reinforcing their focus on additional ophthalmic challenges.

BELKIN Vision made a splash in the glaucoma treatment industry with their fast, no-contact laser. While other glaucoma treatments—such as daily drops or invasive lasers—pose issues of poor patient adherence and significant time requirements, the 

 enhances intraocular fluid drainage in about a second via delivery of a single laser beam to the limbus.

"When we started the company in 2013, we always imagined that it would transport us to the stage we're at today. Now, on the cusp of commercialization, we anticipate a multitude of exciting future applications and wanted to ensure that our company name aligned with that vision. We're confident that BELKIN Vision perfectly reflects our future plans and will capture the hearts and minds of our future customers," said Daria Lemann Blumenthal, CEO of BELKIN Vision.

For more information, visit BELKIN Vision’s 

The glaucoma treatment company rebrands to align more closely with goals and direction of the company.

BELKIN Laser rebrands as BELKIN Vision

The Royal College of Surgeons of Edinburgh (RCSEd), a leading surgical college, announced the launch of its own Membership of the Royal College of Surgeons (MRCS) ophthalmology examination.

This new examination will be available in early 2022, and a Fellowship examination will follow later in the year.

“We would like to thank the ICO for the very positive relationship we have enjoyed over the last few years and wish them the best in their pursuit of improving standards in global Ophthalmology care,” said Professor Michael Griffin OBE, President of the RCSEd. “We are delighted to now have the opportunity to launch our very own MRCS Ophthalmology and look forward to adding a Fellowship examination next year, ensuring those in the profession will have a continued route into College membership.”

RCSEd was first incorporated as the Barber Surgeons of Edinburgh in 1505, and it has since grown to nearly 29,000 members from 100 countries worldwide, with 15,000 in the UK. As one of the oldest surgical corporations in the world, the College promotes the high standards in surgical and dental practice. The College is also home of the UK’s only Faculty of Surgical Trainers, which is open to anyone with interest in surgical training, regardless of College affiliation.

All ICO College Members—including the April intake of this year—are eligible for the full benefits and services the College offers.

A new MRCS ophthalmology examination will be offered to ICO College Members beginning in 2022.

Royal College of Surgeons of Edinburgh launches MRCS ophthalmology exam, Fellowship to follow

Horner’s syndrome is characterised by ipsilateral ptosis, miosis and anhidrosis that result from a lesion affecting the oculosympathetic pathway. The syndrome can be benign if idiopathic or iatrogenic, however, it can also be predictive of a life-threatening event such as demyelinating inflammatory, infectious, vascular or neoplastic problems.

It is important to promptly and accurately diagnose the cause; ophthalmologists are likely to be on the front lines. According to Dr Aaron M. Fairbanks, a senior ophthalmology resident at Mayo Clinic, Rochester, Minnesota, United States, no definitive information is available about the pathologies associated with Horner’s syndrome and the incidence rate in US adults is unknown.

Because no US population-based studies of the syndrome had been undertaken, Dr Fairbanks and his colleagues set out to determine its population-based incidence in adults, evaluate the underlying causes and disease manifestations, and investigate the value of imaging in patients with a neurologically isolated Horner’s syndrome.

Uveitis: A leading and underestimated cause of visual morbidity in patients

The investigators conducted a retrospective chart review of all adults diagnosed with Horner’s syndrome in Olmsted County, Minnesota, using the Rochester Epidemiology Project database, between 1 January 2000 and 31 December 2018. According to Dr Fairbanks, the team of investigators reviewed the charts for the correct diagnoses, and recorded the patient demographic data, presenting signs and symptoms, imaging results and aetiologies, and analysed all the results.

Of the 736 patients identified in the review of cases, 78 confirmed cases were included in the study; the rest were excluded because of their non-resident status, disease onset outside the study time frame, or miscoded or incorrect diagnoses.

According to the team of investigators, the causes varied widely from those that were benign, including idiopathic and surgical causes, cluster headache and goitre, to neurologically or systemically dangerous causes including carotid artery dissection; stroke; neoplastic and traumatic causes; varicella zoster; arteriovenous fistula; and fibromuscular dysplasia.

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The median patient age was 57 years and all patients were white. The age- and sex-adjusted incidence of Horner’s syndrome during the study period was 4.24/100,000/year with no difference in sex or over time.

“We did find a significant [P < 0.001] difference across age groups, with older patients having a higher incidence of Horner’s syndrome,” Dr Fairbanks pointed out. Three-quarters of cases were diagnosed by neurologists and ophthalmologists, with most diagnosed clinically. “Interestingly,” Dr Fairbanks said, “idiopathic cases were more likely to be confirmed with cocaine or apraclonidine eyedrop testing (P = 0.002), and stroke, surgical and dangerous causes were more often diagnosed clinically (P = 0.008).”

The most common aetiologies were idiopathic (20 patients, 25.6%), followed by internal carotidartery (ICA) dissection (15 patients, 19.2%), stroke (12 patients, 15.4%), surgical (12 patients, 15.4%) and neoplastic (11.5%). Analysis of the aetiologies indicated that about 56% of cases had a dangerous neurological or systemic origin, according to investigators.

Compared with other aetiologies, the patients with ICA dissections—which were more likely to be diagnosed in younger individuals with a mean age of 49 years (P = 0.02)—were more likely to have pain (P < 0.001), facial paraesthesia (P = 0.007), blurred vision (P = 0.04) and photophobia (P < 0.004). Most of the cases with a stroke had a lateral medullary infarction.

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Neoplastic causes included four Pancoast tumours that affected the oculosympathetic pathway at the lung apex. It was noted that the most common neoplasm was lung cancer.

Moreover, as Dr Fairbanks explained, the investigators found that neuroimaging results were surprising in that almost 40% of patients with a neurologically isolated Horner’s syndrome had a positive finding on computed tomography (CT) or magnetic resonance imaging (MRI). Dr Fairbanks went on to note that in isolated Horner’s syndrome cases, pain suggested both a dangerous aetiology and a positive imaging result, which was driven primarily by patients found to have an ICA dissection.

In this first US population-based study of the incidence of Horner’s syndrome, the primary take-home point is that 56.4% of cases resulted from a dangerous cause; in previous reports the percentages ranged from 8% to 78%. Another finding useful in diagnosis is that about 40% of patients with an isolated Horner’s syndrome had positive CT or MRI findings, which is almost double the percentage reported previously.

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Finally, investigators noted that pain reported by patients suggested a dangerous aetiology and positive imaging, which in this study was most likely to be secondary to an ICA dissection. Ophthalmologists should keep in mind that ICA dissections are likely to occur in younger patients, may look like an isolated syndrome or present with neurological disease and stroke, are painful, and may cause facial paraesthesia, blurred vision or photophobia, compared with other causes.

“We recommend imaging of the oculosympathetic pathway in all cases of Horner’s syndrome without a clear aetiology, even in neurologically isolated cases, particularly when pain is present,” Dr Fairbanks emphasised.

This article is adapted from Dr Fairbanks’ presentation at the American Academy of Ophthalmology’s virtual annual meeting. Dr Fairbanks has no financial interest in this subject matter.

Investigators found that 56.4% of Horner’s syndrome cases resulted from a dangerous cause. 

Shedding light on Horner’s syndrome

Surgery in a patient with uveitis presents a number of challenges. First, the visual outcomes of surgery are likely to be worse than in patients without uveitis. The procedure may also be more prone to uveitis-related surgical complications, such as damage to the cornea, iris atrophy or posterior synechiae, cystoid macular oedema (CMO) and epiretinal membranes. Finally, there is also a risk of uveitis recurrence after surgery, even in a patient whose disease had previously been well controlled. The risks of surgery vary greatly, depending on the type and severity of uveitis, the type of surgery required and the patient’s general health and comorbid conditions.

In this article, I will primarily discuss cataract surgery, as it is the surgical procedure most frequently performed in patients with uveitis and the one on which protocols for other types of surgery are based.

The first principle of surgery in patients with uveitis is that their uveitis should be completely and consistently controlled for at least 3 months prior to surgery. This objective is typically easier to achieve prior to an elective procedure like cataract surgery than an emergency repair of a retinal detachment. However, if the situation is urgent in some types of lens-induced uveitis, the surgeon may not have the luxury of waiting for complete and consistent control.

Strategies for controlling inflammation become increasingly aggressive with more severe uveitis. Certain uveitic conditions, including Fuchs uveitis syndrome, do very well with cataract surgery and may not even need extra perioperative steroids. A patient with a history of recurrent acute anterior uveitis that is well controlled with topical steroids, with no recent flareups, may also fare quite well. In these patients, I typically increase the dose of topical steroid (prednisolone acetate 1% every 2 hours), starting a couple of days before surgery and continuing for a month after surgery, tapering back to baseline based on postoperative inflammation. The risk of CMO can peak 3 to 4 weeks after surgery, so it is important not to stop the steroids too soon. I also add a topical NSAID such as bromfenac or ketorolac, provided there is no medical contraindication. NSAIDs significantly reduce the risk of pseudophakic CMO

 and should always be on board in patients with uveitis, even if the surgeon does not use them in routine cataract cases.

Investigators analyse factors associated with patient satisfaction after refractive surgery

In those with any posterior involvement, including significant posterior synechiae, recent sarcoid panuveitis or Behçet’s disease, or any history of macular oedema, much more aggressive measures may be needed. These patients may require regional steroid injections, systemic steroids, and/or systemic immunosuppression—essentially, whatever it takes to control the uveitis before surgery. Although I may give patients a sub-Tenon’s triamcinolone acetonide injection or intravenous steroids at the time of surgery, I generally prefer to also have steroids on board before the day of surgery.

For control of uveitis perioperatively, an intravitreal injection of the dexamethasone intravitreal implant 0.7 mg (Ozurdex, Allergan) or preservative-free triamcinolone acetonide 2–4 mg 2 to 4 weeks prior to surgery is indicated. Remember that intravitreal triamcinolone is opaque and may blur the retinal reflex if it is still in the eye at the time of surgery. If the patient does have an intraocular pressure (IOP) response to the steroid, it typically lasts no more than 2 to 4 months and may be controlled with glaucoma drops.

A longer-lasting implant such as injectable fluocinolone acetonide 0.18 mg (Yutiq, EyePoint Pharmaceuticals) or fluocinolone acetonide 0.59 mg scleral-fixated implant (Retisert, Bausch + Lomb), may be beneficial in a patient who has had local injections in the past and is not a steroid responder. Retisert requires surgical implantation, whereas Yutiq is administered via an in-office injection through a 25-gauge siliconised needle. 

With the longer-duration implants, the patient may have adequate steroid coverage to not only control postoperative CMO but to prevent recurrences of uveitis and macular oedema for several years after surgery. We also have to consider the dose and location of these steroids. Yutiq contains about one-third the dose of fluocinolone acetonide that Retisert does (0.18 mg vs 0.59 mg), and because it sits more posteriorly in the eye, further from the ciliary body, may have a lower risk of inducing glaucoma.

Studies suggest that long-lasting intravitreal steroids can be as effective as immunosuppressive therapy in controlling uveitis and macular oedema,

 so these are a great option for patients who cannot take oral steroids because of diabetes or high blood pressure, who are medically unable to take immunosuppressive therapy, or who would prefer to avoid these drugs.

Systemic immunosuppressants and local steroids can work very well in combination. For example, if the patient is already well controlled on a single immunosuppressant, I do not usually add another immunosuppressant just for cataract surgery. Rather, I will use steroids in some form as adjunctive therapy.

Being prepared to manage a small pupil is essential when performing cataract surgery in patients with uveitis, as these patients often have synechiae or iris atrophy. In some cases, manual iris stretching techniques may be sufficient, but iris hooks or pupil expansion rings are often required. Iris hooks take more time to place and may cause damage to the iris if placed incorrectly, but they provide a great deal of flexibility. If I run into an intraoperative complication such as zonular dehiscence or a nuclear fragment that is floating peripherally and is difficult to visualise, iris hooks allow me to expand the pupil more in that particular meridian. 

Controlling postop pain, inflammation in cataract patients: drug delivery vs drops (video)

A Malyugin ring, by contrast, provides a fixed pupil size and is a larger piece of hardware that can complicate other aspects of the surgery. However, it is fast and easy to place and a large study suggested that the Malyugin ring and iris hooks are comparably effective.

 In retinal surgery, performing scleral depression and getting a really good view of the peripheral retina will likely be easier with hooks than with a ring. Anyone who performs surgery in uveitic eyes should be comfortable with both types of device.

A femtosecond laser can make cataract surgery easier in uveitic eyes with poor zonular support. However, a FLACS procedure also requires a longer duration of pupil dilation, which can be quite challenging in these eyes. Even with good dilation, it may be more difficult to achieve the laser capsulotomy, as blood from stretching the pupil may affect the focusing ability of the laser. For all these reasons, I typically opt for manual capsulorrhexis and phaco in my patients with uveitis.

Phaco power modulation boosts safety, efficacy in cataract surgery

Postoperatively, these patients may need aggressive cycloplegic therapy to prevent recurrent posterior synechiae. If synechiae do occur, I prefer to intervene quickly to avoid pupillary glaucoma. Unlike many routine cataract surgeries, the postoperative care for patients with uveitis should not be delegated to other clinicians. It is important to monitor carefully for any signs of inflammation or increased IOP, and to be sure to check both eyes in patients with bilateral uveitis, rather than just the operative eye.

The outcomes of cataract surgery with a lens implant in several types of uveitis, including juvenile rheumatoid arthritis-associated uveitis, Behçet’s disease panuveitis and Vogt-Koyanagi-Harada disease, can be very disappointing. In some cases, the surgery seems to go well, but the vision just does not improve as much as expected. This may be due to an unrecognised retinal complication, such as an epiretinal membrane or a tractional detachment that could not be seen on preoperative imaging through a dense cataract, but in some cases there is no clear explanation for the poor result. Those with comorbid conditions (e.g. cataract + glaucoma + uveitis) may require multiple, staged procedures to achieve a satisfactory final visual result.

FDA accepts Bausch Health, Clearside Biomedical's resubmitted Xipere NDA

For all these reasons, good patient education is absolutely critical to avoid postoperative dissatisfaction. Patients with uveitis often develop early cataract and may therefore be younger and of working age, and may still have residual accommodation that will be lost after surgery. They have a higher risk of complications and a longer recovery period than non-uveitis cataract patients, so it is important to under-promise (and, hopefully, over-deliver). Patients need to know that they probably will not see 20/20 in the waiting room like their uncle Fred did after his cataract surgery last year. That said, I personally find it more satisfying to give a person with hand-motion vision a 20/40 visual outcome than to improve a routine 20/25 cataract patient to 20/20. With carefully individualised care, we can optimise the chance of good outcomes for our patients with uveitis.

Dr Dunn is a retina and uveitis specialist at Wills Eye Hospital in Philadelphia, Pennsylvania, and has a particular interest in cataract surgery in patients with uveitis. He has no financial disclosures to report. Contact him at 

1. Wielders LHP, Lamermont VA, Schouten JSAG, et al. Prevention of cystoid macular edema after cataract surgery in nondiabetic and diabetic patients: A systematic review and meta-analysis. 

2. Jaffe GJ, Pavesio CE, Study investigators. Effect of a fluocinolone acetonide insert on recurrence rates in noninfectious intermediate, posterior, or panuveitis: Three-year results. 

3. Eyepoint Pharmaceuticals, Inc. Full Prescribing Information. Yutiq.com. 

https://eyepointpharma.com/wp-content/uploads/2019/01/YUTIQ-USPI-20181120.pdf

4. Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group; Kempen JH, Altaweel MM, Drye LT, et al. Benefits of systemic anti-inflammatory therapy versus fluocinolone acetonide intraocular implant for intermediate uveitis, posterior uveitis, and panuveitis: 54-month results of the Multicenter Uveitis Steroid Treatment Trial and follow-up study. Ophthalmology 2015;122(10):1967-75.

5. Balal S, Jbari AS, Nitiapapand R, et al. Management and outcomes of the small pupil in cataract surgery: Iris hooks, Malyugin ring or phenylephrine? 

While operating on a patient with chronic uveitis presents some challenges, there are a few pearls that may increase success.

Pearls for ocular surgical success in patients with chronic uveitis

We’ll now move forward and speak briefly about anti-VEGF therapy in general. Dr Peto, can you briefly discuss how anti-VEGF drugs have become the mainstay of therapy for so many retinal diseases? What’s the mechanism of action, and why are those drugs so successful?

 These drugs have become very successful because they give the patients hope. We can tell them for the first time that their vision is likely to improve, or at least be stabilized, and there’s only a very small chance that they’ll get much worse and a chance that they’ll get slowly worse if the drug doesn’t work in their eyes. The patients really respond to this, although most times they’re very afraid of the first injections.

In terms of regimens, we try to start the injections on the same day if we can. There’s nothing worse than for them to go home, google or watch a movie, and try to first show we’re going to put the injection in. The patients are very responsive to this care that they receive. We’ve been disadvantaged in the diabetes field by having to prioritize the patients with AMD [age-related macular degeneration] at the beginning of the pandemic, because AMD takes the vision away much quicker than diabetic macular edema. When we had limited footfall, the patients with AMD were injected as a priority. But we know that patients with diabetes need to be treated as well so they’re back on track.

Because we go into the eye, the endophthalmitis is always a risk. It might be different in different units depending on how this physical setup is. We do find that nurses in our units are very good injectors. They usually take very good care of the patient. They have their lists, they get to know these patients who come back, and they’re very good at managing patients with anxiety as well. For us, the nurse injectors—and in some units optometrists and orthoptist injectors—have been a real answer to the question, because we don’t have enough ophthalmologists practically anywhere in the world to deliver this many injections. Of course, ophthalmologists are a lot of the times better used for doing the actual operations or delivering more complicated injections, such as the subretinal injections for gene therapy.

Thank you very much. It’s unique for the United Kingdom and your country [Northern Ireland] for the nurses to be doing the injections. This is not the case in our country. It’s also not the case in France, as far as I know. Dr Korobelnik, there are some more drawbacks. Monthly injections are not the way to go for the next 10 years or so, and the increasing risk of infection with so many injections also exists. In addition to this, we have a big burden to the patient and to the caregivers, especially in working-age people, such as patients with diabetes. Can you give a few words on this as well?

 You’re absolutely right. The burden of those diseases is really high because the patients require frequent visits for control and examination, for injections, and to control their disease. For some patients, we may expand the interval between the injections, and it can become somehow comfortable. Some other patients require extremely frequent injections, and they may require injections in both eyes because quite often in wet AMD and DME [diabetic macular edema] the disease is bilateral. The burden is high for the patients, for their families, and the cost also is quite high because you need to pay for everything: the procedure, the drug, transportation, many things. This will vary a lot from 1 country to another, but it’s adding to the time spent by the patient and their family to come attend the appointments. The burden is very high at the moment, and it’s also a problem for us because we have to cope with all those patients, the ones we’re following and the new ones. As people are living longer, diabetes is becoming more common. We have many more new cases of advanced AMD and diabetic retinopathy. Not only is the burden high for the patients to come, but the pressure is high on us to organize our clinics to deal with all those patients.

Drawbacks and challenges associated with the administration of anti-VEGF injections currently available to treat retinal diseases.

Anti-VEGF Therapy for Retinal Disease

We have to move forward. I’d like to ask Dr Moosajee for her opinion on the treatment options for inherited diseases.

Mariya Moosajee, MBBS, BSc, PhD, FRCOphth:

 Thank you. There aren’t many treatment options for patients with IRD [inherited retinal disease]. Conservative management is important; we give a lot of advice about the diet of these patients, such as fresh fruits and vegetables. We know from studies in animal models that there are high levels of oxidative stress in the retina. Therefore, we’re advocating that patients eat fruits that are red, blue, and black and that are rich in antioxidants, such as grapes, raspberries, pomegranates, and strawberries. We ask patients to wear UV [ultraviolet] sunglasses in bright light to protect the retina from any further sun damage. In a lot of IRDs, you can get macular edema; those patients may be put on Diamox [acetazolamide] or Trusopt [dorzolamide] just to help manage that. But we now have the first approved retinal gene therapy targeted toward gene 

, which causes leber congenital amaurosis phenotype and also retinitis pigmentosa. This is called voretigene neparvovec and is widely available across the world. I’ve the seen the results of some of the real-life patients being treated with this, especially in the pediatric cohort. We’re seeing increases in best-corrected visual acuity and improvements in the navigational vision and in the vision in dim light. There are some inherited retinal diseases, such as gyrate atrophy, which is an autosomal recessive disease caused by mutations in the 

 gene. This encodes an enzyme that’s active in our mitochondria to help break down ornithine. If we identify these mutations and we also advise our patients to take a diet that’s arginine restricted to reduce ornithine intake, this can potentially prevent further retinal degeneration. There are several clinical trials underway for gene replacement therapies; we’re hoping to see an increase in availability of treatments to this cohort of patients in the coming years.

Thank you. Maybe you can add a little bit on subretinal injection of gene therapy since we are already speaking about gene therapy in inherited diseases.

Dr Mariya Moosajee highlights therapies approved as well as under study to improve treatment for patients with inherited retinal disease.

Pearls for ocular surgical success in patients with chronic uveitis

Anti-VEGF Therapy for Retinal Disease

Inherited Retinal Disease: Treatment Overview