Feature, Report

Ophthalmology Updates! – Part 2

Associate Professor Adrian Fung’s Ophthalmology Updates! Conference series reached new heights in its fourth year. In the second and final part of his report, Lewis Williams provides a recap of the event’s presentations.

The ongoing success of the Ophthalmology Updates! series has confirmed its role in the Australian conference marketplace, and tentative dates for the next event next have been set for August 29 and 30, 2020.

Once again, each presenter at the 2019 conference followed a set format of detailing a common condition, frontier cases’ that proved challenging or required a novel approach, and illustrative case reports.

Uveitis – Acute retinal necrosis

Peter McCluskey

Professor Peter McCluskey is Director of the Save Sight Institute at Sydney Eye Hospital and Professor of Ophthalmology at the University of Sydney. He also holds a position at Sydney’s St Vincent’s Hospital. His sub-specialties are inflammatory eye disease and cataract surgery; two conditions that sometimes collide and result in significant challenges.

Acute retinal necrosis (ARN) is a rare (0.63 cases per million), destructive infectious retinitis with rapid onset that was first described in the late 1970s. Since the 1980s the most common cause is HSVI or HSVII, although the varicella-zoster virus (VZV) is also a possibility. Up to 20% of cases are associated with a CNS encephalitis attributable to HSVI or HSVII.

Interestingly, the age of onset also depends on the causative organism, with VZV occurring in older populations and HSVII in younger groups. However, the prevalence data spread is quite broad, and age alone is not indicative of the virus involved.

Despite the virus connection, up to 50% of cases are classified as idiopathic. Only 20% are infective (mostly herpetic) and 30% are inflammatory in origin. The idiopathic classification also embraces those cases associated with Fuch’s corneal endothelial dystrophy and white dot syndromes (WDS) that affect the outer retina, the RPE, choriocapillaris, and choroid, or some combination of those.

An inflammatory classification can include HLA B27/systemic B27, sarcoid, Behҫet disease, TB, toxoplasmosis, and the great mimic – syphilis. In patients that are very immunosuppressed, the retina is destroyed rapidly. Generally, ARN can happen in those who are normal or immunosuppressed, and the sudden onset and rapid progression means the window for treatment can be small.

Furthermore, the severity can be variable. Additionally, the risk of a RD and the possibility of the fellow eye becoming involved are both high. The possibility of a pan-uveitis (multifocal and spreading) developing must also be considered with a triad of signs – peripheral retinitis, vasculitis, and optic neuropathy all possible. A differential diagnosis of ARN from cytomegalovirus retinitis (CMV retinitis) might also be required.

Generally, ARN occurs in a normal patient with a sudden onset and results in an inflamed eye/infective endophthalmitis or occurs in those with a known history of Behҫet disease, TB, toxoplasmosis, or syphilis. CMV retinitis has an insidious onset and is usually asymptomatic; the eye is quiet, the ocular media clear, and the patient is likely to be immunosuppressed or suffering from HIV (15-40% of cases).

Characteristically, the retinal signs are described as ‘pizza fundus’. Differentiation requires multi-modal imaging, careful monitoring of the fellow eye, a careful history, and a thorough, comprehensive eye examination with targeted investigations. Syphilis should always be considered as a cause and eliminated early. An OCT can help differentiate viral and toxoplasmosis cases because the latter causes choroidal shadowing and disruption.

ARN treatment must cover the possibility of acute blinding, and a ‘tap & inject’ might be needed. Intravitreal antivirals, antibiotics, and antifungals separately, or in some combination, might be required. Systemic valtrex/acyclovir, ciproxin, or voriconazole and high-dose oral steroids also could be necessary.

The literature suggests that there are few differences between the oral and intravitreal approaches to medication. Laser demarcation might be useful to contain the condition and reduce the risk of rhegmatogenous RD, but the evidence is not strong. About 10% of cases became bilateral, about half end up with reduced vision, and about 63% experience a RD. PCR remains the standard for a definitive diagnosis. Severe vision loss is still common.

Neuro-ophthalmology: Neurological ptosis

Clare Fraser

Associate Professor Clare Fraser from the University of Sydney delivered a solid, informative, and engaging lecture on neurological ptosis.

When presented with a ptosis case, her first piece of advice was to seek old photographs of the patient and quiz family members regarding their observations of the patient’s eyes, head posture, physical activity, general appearance, and so on.

If the ptosis is unilateral, first thoughts should turn to Horner’s syndrome, 3rd Nerve palsy, or a tumour. If the condition is bilateral, especially if symmetrical, chronic progressive external ophthalmoplegia is the most likely issue. Other causes, such as aponeurotic, congenital, neurogenic, myogenic, or neuromuscular/mechanical (floppy eyelids), are possible. Myasthenia gravis (MG), a chronic, autoimmune, neuro-muscular junction problem, is also a possibility.

The demographics of MG are interesting. Females are likely to present in their 3-4th decade, whereas males are more likely to present in their 6-7th decade.

Importantly, ocular symptoms are the first presenting sign in about 70% of cases. Furthermore, 50% of ocular MG (OMG) patients progress to the systemic version of the disease, although the data varies widely depending on the source (12%-65%).

Clinical signs are muscle weakness and fatigability due to antibodies working against post-synaptic nicotinic ACh receptors at neuro-muscular junctions. That reduction in ACh receptors is the root cause of the signs and symptoms.

A patient history might reveal a fatigable ptosis and/or diplopia immediately upon awakening. Crucial to the management of the condition is information relating to the speed of onset and any difficulty with speech, swallowing, or breathing.

Medications can include lithium compounds, beta-blockers, statins, and botox. The practitioner also needs to be alert to the possibility of thyroid and other autoimmune symptoms.

Unfortunately, MG can be mimicked by other conditions, such as Miller-Fisher and Eaton-Lambert syndromes, or too much cosmetic botox.

Other ocular features that might be noted include: variable performance of the EOMs, weak orbicularis oculi muscles, fatigability more generally, Cogan’s lid twitch (the patient looks down for 20 seconds then back to eye level – one or both lid overshoots upwards and then drifts [droops/twitches] downwards [fatigue] while eye-level fixation is maintained), and altered saccades.

Signs and symptoms never involved are pupil behaviour, pain, and numbness. Fatigability can be disclosed by worsening ptosis and/or a downward drift of the eye position, or a gradual reduction in movement amplitude during repeated horizontal eye excursions.

General aspects that warrant investigation include: neck strength (flexion and extension), arm strength and fatigability, hip flexion, and the simple act of getting out of a chair.

A simple test to apply is the ice test, in which ice cubes (contained in a disposable glove) or a cool pack are applied to the closed lids for 2 min. A 2 mm improvement in ptosis is indicative, as is an improvement in ocular motility. The improvement is due to a low-temperature-induced reduction in acetylcholinesterase (AChE) activity at the neuro-muscular junctions leaving more ACh still active.

Other tests include various blood tests, CT/MRI of the chest (looking for thymoma), and what is widely regarded as the gold standard: single-fibre electromyography (EMG)

Medications include the anti-AChE pyridostigmine and steroids that can precipitate a crisis, which might require a neurology consult. A thymectomy is possible if a thymoma is detected.

Other treatments include ptosis surgery in severe and unresponsive cases, but only after stability of the condition has been demonstrated for at least 6 months. However, ptosis surgery can result in corneal exposure.

There is only weak evidence supporting the suspicion that the use of statins can induce MG, however several drugs other than botox can affect MG. They include: aminoglycosides, lithium compounds, phenytoin, Ca-channel blockers, beta-blockers, chloroquine, and gabapentin.

Differential diagnoses are required for other cranial nerve or brainstem diseases, Miller-Fisher syndrome, CPEO, Kearns-Sayer syndrome, myotonic dystrophy, oculopharyngeal dystrophy, Eaton-Lambert syndrome, and botulism (not of the injected type).

Fraser summarised her presentation as: involve a neurologist, the risk of systemic involvement is greatest in the first 2 years after diagnosis of OMG, there are systemic associations with the thyroid, and treatment options include pyridostigmine, steroids, immunosuppressants, and a thymectomy. Symptom management using patching for diplopia and a ptosis prop enable postponing surgery until the condition is stable.

Ocular hypertension

Paul Healey

Clinical Associate Professor Paul Healey holds positions with the University of Sydney (Sydney Eye Hospital, Westmead Hospital) as well as in various private practices. He is also the glaucoma specialist investigator for the Blue Mountains Eye Study.

He opened his presentation by defining what ocular hypertension (OHT) is not. That is, it is not glaucoma, angle-closure glaucoma, a steroid response, nor is it secondary to pseudoexfoliation syndrome (PXF), the most common cause of secondary glaucoma.

He made it clear that when he spoke of ocular hypertension he was referring to primary ocular hypertension (POHT), which he defined as an eye with an IOP more than 2 standard deviations (SDs) above the population mean. Unlike secondary OHT, POHT has no known cause and the patient has no history of IOP rising substantially.

NSW data suggests that the mean IOP is 16 mm Hg and 2 SDs. That data takes the POHT threshold to 22 mm Hg. He estimated that 3-4% of the population has POHT, but ethnicity is relevant. Japanese estimates for their population put the prevalence of POHT at just 0.8% using a different definition based on a mean IOP of 14 mm Hg.

Based on an Indian study (The Chennai Eye Study), Healey noted that if OHT is detected at the first eye examination, OHT is usually found subsequently. Glaucoma and POHT have similar risk factors including age, higher IOPs, larger cup-disc ratios, higher pattern SDs, and thinner central corneal thicknesses.

In the US-based Ocular Hypertension Treatment Study (OHTS), the IOP of the control (observation only) group decreased at the five-year mark, but the decrease due to medications used in the treatment group resulted in greater IOP reductions and bigger differences. At year five, 9.5% of the control group had developed glaucoma and 4.4% of the treatment group had converted to glaucoma. At the study’s end (year 13), 22% of the controls and 16% of the treatment group had glaucoma. Most of those with POAG had manifest optic disc differences, but not differences in vision.

Ethnic differences are known. For example, African Americans have a higher incidence of glaucoma than white Americans (6.9% and 3.6% respectively). Central corneal thickness (CCT) is a key feature and generally, Caucasians have thicker corneas. Thinner corneas have an increased hazard ratio. Surprisingly, alterations to the visual fields responded poorly to medication, even when large IOP reductions were achieved.

It has been suggested that CCT is much more important than IOP. Many POHT cases actually already have glaucoma, and even a 20% IOP reduction is inadequate to prevent a conversion from POHT to POAG.

The % reduction in IOP that should be aimed for depends largely on what the starting point is. If IOP is 16 mm Hg, for example, aiming for a 1 SD reduction is reasonable.

Healey also stated that if a ‘POHT’ case exhibits disc haemorrhages, it is reasonable to change the diagnosis to glaucoma. However, he also noted that it was easy for disc haemorrhages to be missed, especially if subtle.

The presence of a disc haemorrhage suggests a much higher risk of glaucoma, although in normal tension glaucoma (NTG) the situation is less clear cut. He described disc haemorrhages as a result of ripped optic disc capillaries due to glaucomatous disc changes that occur throughout glaucoma.

It was also noted that taking prostaglandins thins corneas. Patients whose CCTs lie outside the range 500 to 580 microns should be investigated more thoroughly, although the normal diurnal variation in CCT is a confounding factor.

To the glaucoma specialist, Healey referred to the use of non-Goldmann tonometers as a ‘complication’, stating that ophthalmologists use a Goldmann applanation tonometer for consistency when assessing risk. It seems that, despite the significant numbers of NTG cases in the population and other better correlated tests for glaucoma, the predicted demise of tonometry is somewhat premature.