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Report, Research

Ophthalmology updates! 2018

31/10/2018By Lewis Williams PhD
Ophthalmology Updates! has returned, with its unique combination of practical refreshers and pioneering ‘frontier’ topics. LEWIS WILLIAMS’ special two-part report delves into both aspects of the presentations delivered at this year’s iteration of the growing conference.

The most recent Ophthalmology Updates! two-day conference convened by vitreoretinal surgeon and macular disease ophthalmologist, Associate Professor Adrian Fung, was held at Sydney’s Westin Hotel in late August. True to form, the faculty maintained the high standard set by earlier incarnations of the meeting and the delegates were well served by the program.

Delegates were ophthalmologists, ophthalmology registrars, and medical practitioners contemplating a career in ophthalmology. Each presentation followed the well-established pattern of a common condition within a sub-discipline, a ‘frontier’ or novel application/idea within that sub-discipline, and some clinical cases to illustrate the sub-discipline.


Oculoplastic surgeon Dr Peter Martin, Head of the Oculoplastics Unit at Sydney Eye Hospital, the New Children’s Hospital, Westmead, and Sydney Children’s Hospital, Randwick, gave a profusely illustrated presentation on ectropion (common condition) as well as the use of Botox in appropriate cases (frontier/novel). He then illustrated his talk with several relevant clinical cases.

Martin defined ectropion as an abnormal eversion of the eyelid from the globe. Lid abnormalities such as ectropion and entropion are the result of the interactions between the levator aponeurosis (vertical retractors which can be subject to disinsertion), superior transverse ligament/ capsulopalpebral fascia, tarsi, and the medial and lateral canthal ligaments. Gravity aided by lid laxity and lid anatomy is a major contributor ectropion, whereas entropion is more likely to be due to lid retractor laxity. Applying gentle finger pressure to push the lid up can test inferior retractor stability.

Involutional ectropion is usually an age-related change but other causes include cicatricial (trauma, UV, surgical, skin diseases, chemical/thermal burns), 7th N palsy, mechanical (weight of a tumour, lid oedema, fat pads), and less commonly, congenital facial dysmorphic syndromes often due to a vertical shortage of skin.

Involutional and cicatricial are the two most common forms of ectropion in which the primary aetiological factors are horizontal eyelid laxity (involving all lid tissues), problems with the orbicularis oculi muscle (OOM), the inferior retractors, and/or the tarsal plate.

Symptoms include epiphora, superficial punctate keratopathy (SPK), foreign body sensation, conjunctival exposure and keratinisation, tarsal and conjunctival thickening, photophobia, and recurrent infection and discharge. Skin tightness can be assessed simply by gentle traction to differentiate between adequate or a shortage of skin. Jaw opening/actuation can also reveal useful information.

Ectropion can involve the whole lid or just the medial or lateral aspects only. A simple snap test involving a gentle squeezing and pulling outwards of the lower lid skin just below the lash line, followed by release of the lid while monitoring the speed and uniformity of return, can be instructive. Likewise, a similar pulling of the medial (inwards) or lateral (outwards) aspect of the lids is useful in assessing canthal tendon laxity.

Martin then went on to show videos of the various techniques applicable to those cases with adequate quantities of tissue present. If an inadequate amount is present then either a lengthening procedure or a skin graft is required. Donor tissue sites include post or preauricular skin, the upper lid (or the contralateral lower lid equivalent area if the problem is unilateral), supraclavicular, or the inner arm.

Paralytic ectropion is often more difficult to deal with depending on the severity of the condition and permanent solutions should not be instigated until at least 6 months after diagnosis or stability has been reached.

Botulinum toxin (BTX) has long been used as an alternative to strabismus surgery but that led logically to treatment for other neuromuscular conditions, such as blepharospasm and in oculoplastic applications. BTX effects last 4–6 months with only minor side-effects in most patients.

Allergan released BTX (under the Botox tradename, other names are used by other manufacturers) for treatment of strabismus, blepharospasm, and hemifacial spasm in 1989. The fabled use of BTX in cosmetic applications (6.3 million procedures expected globally in 2018) followed observations of BTX’s effects on frown lines by an ophthalmologist and a dermatologist in 1991.

However, it was not until 2001 that BTX use was approved by the US FDA. BTX blocks the terminal receptors of cholinergic nerves from releasing acetylcholine thereby producing a functional, albeit temporary, muscle denervation. Current uses range from strabismus to oculoplastics, sweat disorders, various types of headaches and back pain, and thyroid lid retraction.

Initially, resolution of headaches was thought to simply be a case of reduced muscle tension, but it has now been shown to be due to inhibition of the release of nociceptive neurotransmitters in the peripheral nervous system.

Benign essential blepharospasm (BEP) is a condition characterised by abnormal contractions and twitching that can cause eyelid closure for short periods (rendering the person transiently blind with each closure), and which can last for days at a time. While the root cause remains unknown, stress, irritants, or fatigue is believed to play a part.

Other possible ophthalmological uses include a BTX-induced tarsorrhaphy in the treatment of MK, neurotrophic ulcers, and exposure keratopathy. It is also useful in cases of thyroid lid retraction that can improve the appearance of patients, decrease lubricant usage, and reduce the degree of fibrosis that can result. Unfortunately, in 10–20% of cases, transient diplopia and ptosis can occur.


Professor Gerard Sutton, inaugural Professor of Corneal and Refractive Surgery at the Sydney Eye Hospital and the University of Sydney delivered a presentation on recurrent corneal erosions (RCEs) for his common condition and corneal bioengineering for his frontier topic.

RCE has a mean age at presentation of 44.5 years, more than 85% of which are unilateral. The most common cause of the condition is minor trauma, most commonly an errant fingernail. However, other causes include EBMD (epithelial basement membrane dystrophy) and refractive surgery. Almost 20% of cases have an unknown aetiology. Importantly, almost 60% of cases also have MGD. Unsurprisingly, almost 70% of cases occur in the more exposed inferior quadrant of the cornea.

One of the slides Sutton used to illustrate the condition suggested that retro-illumination is as effective, if not more effective, at disclosing the extent of the cornea affected by a RCE.

However, in a later slide, Sutton suggested laser confocal microscopy was better suited to the task. An OCT device equipped with an anterior segment module is also useful.

At the root of the condition is an abnormality of the adherence between the corneal epithelium’s basement membrane and Bowman’s layer due to an abnormal adhesion complex and/or a reduplication of the basement membrane.

Treatment can involve a bandage CL (a SiHy CL where possible), a prophylactic antibiotic with or without the application of an NSAID (e.g., diclofenac), and hypertonic saline ointment. Additional medical treatment can include doxycycline to reduce MMPs and assist any MGD present, and anti-inflammatory fluorometholone eyedrops. The use of autologous blood serum was described as being expensive and unpleasant.

In one study summarised by Sutton in which a bandage CL was compared with ocular lubricants, bandage CLs resolved the condition faster than lubricants (5 vs. 9 weeks). Surgical treatments used in RCEs include anterior stromal puncture, epithelial debridement (manual, diamond burr, or alcohol), and laser-based PTK.

Sutton described his frontier topic, 3D Bio- Engineered Corneas, as being “just around the cornea”. He put the world number of corneal blind at about 10 million, 90% of whom live in developing countries. The major causes of corneal blindness include trachoma, corneal ulceration, xerophthalmia, ophthalmia neonatorum, viral infections, traditional eye medicines, onchocerciasis, leprosy, and ocular trauma.

The attractions of creating a successful biocornea are numerous and include; a large waiting list for corneal transplants (estimated at 12.7 million); only 1 in 70 needing a transplant having access to one; and 53% of the world’s population have no access to transplants. The key requisites for a bioengineered cornea are numerous.

They must be transparent, mechanically robust, permanently biointegratable (no adverse effect on neural networks and mass transport of biological essentials and waste products), immunoneutral, relatively inexpensive, and compatible with GMPs.

Some overseas clinical trials commenced in 2010 have met with some success and further trials are ongoing. An Australian corneal bioengineering program is underway with input and involvement from the USyd, the NSW Organ and Tissue Donation Service, and UWollongong. Their endeavours are founded on the use of discarded donor human corneal tissue rendered acellular, as the inclusion of cells in a man-made cornea remains a challenge.

While stromal and epithelial cells can be cultured successfully, the final requirements for a useable cornea are more complex, e.g. fibroblasts need communication with the epithelium to thrive. Induced pluripotent stem cells (iPSCs) in vitro have been used successfully to create corneal organoids containing all the component cell types in a stable system, but the research has a long way to go before human clinical trials can be undertaken.

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Other methods being trialled include moulding, electrospinning (silk-based), and bioprinting (inkjet-like technology, extrusion, and laser-based printing) with and without cross-linking. Sutton sees the research as being likely to expand the future roles played by eye banks, wherein they become bioengineers and ‘printers’ of customised corneas. Projected figures suggest that a bioengineered cornea could be less than 25% of the cost of a procured donor cornea.

Sutton then went on to discuss another of his team’s outputs – the iFixInk and iFixPen system of dispensing a wound-healing bioink. The human-derived, transparent iFixInk promotes stratification of corneal epithelial cell lines, is biocompatible, biodegradable, xenogeneic-free, and cost-effective. Possible uses include corneal ulcers, corneal wounds, and post-corneal surgery treatments.


Neuro-ophthalmologist Dr Clare Fraser first spoke about optic disc drusen and then moved to idiopathic intracranial hypertension as the frontier topic. She described optic disc drusen (ODD) as acellular deposits of calcium, amino and nucleic acids, and mucopolysaccharides that reside in front of the lamina cribrosa.

They are usually bilateral and occur in 0.3–2.4% of the population. Genetically, Fraser characterised them as irregular, dominant inheritance but with incomplete penetrance.

ODD is regarded as important because of its ability to cause visual field defects, mimic papilloedema, anterior ischemic optic neuropathy (AION) and vascular occlusions, and possible involvement in disc axonal compression and ischaemia.

The drusen can be buried deeply in the optic disc or be more superficial.

The root cause is believed to be a genetic predisposition but the actual pathogenesis has not been resolved beyond two classical theories that have calcification of cell mitochondria in common. There are various detection methods, however all have limitations.

B-Scan ultrasonography detects only calcified or large ODD and considerable analytic skill is needed, while a CT scan detects only calcified ODD, the resolution can be inadequate, and the application of radiation is involved. Fundus autofluorescence unreliable with deeper ODD, SD-OCT is expensive and not reliable when deep ODD involved, and EDI-OCT is expensive and interpretation is challenging.

ODD can progress starting with a transition phase in early adulthood that can result in a superficial location for a lesion buried previously. Visual field defects are often detectable by the age of 14 years, but central vision is usually preserved.

Visual field loss in ODD tends to progress slowly. When perimetry is performed, the two nasal quadrants are most affected (>30% each) while the temporal quadrants are affected least (>17% each). However, drusen volume rather than their location is the most influential factor in field defect causation.

Fraser concluded that ODD are relatively common but not always benign, SS or EDI-OCT were the best methods of imaging except when deep or uncalcified, and their size matters.

Idiopathic intracranial hypertension (IIH) is a condition that often needs to be differentiated from ODD, and Fraser also questioned whether IIH really is idiopathic.

Diagnostically, IIH has signs and symptoms of headaches, nausea, vomiting, transient visual obscurations (TVOs), and papilloedema. Except in sixth nerve palsies, there are no localised neurological signs. The CSF opening pressure is >25 cm (water) but the CSF’s constituents are normal. Neuroimaging is usually normal. Usually, no other underlying causes are identifiable.

Current theories centre on obesity and sleep apnoea, and the mild increase in cerebrospinal fluid (CSF) pressure that can result from dural incompetence or venous narrowing. Increased venous pressure can increase CSF pressure further.

Overall, stenting can resolve many of the symptoms IIH induces but complications are possible and stenting should not be regarded as the first line of treatment (weight loss alone is usually sufficient). Complications include headaches, recurring stenosis (in the stent or adjacent to it), systemic complications, sinus thrombosis, intracranial haemorrhage, and in rare cases death.

Research has determined that the amount of truncal fat correlated with intracranial pressure and weight loss that was the most effective in reducing IIH came from the trunk. If necessary, bariatric surgery as a weight loss measure has proved to be the most effective, cost-effective, and sustained. Management was summarised as: alleviate symptoms (e.g. headache) and preserve vision while the patient loses weight.

Cataract surgery

Macquarie University Hospital’s Associate Professor Chandra Bala raised the question applicable to an unwanted refractive outcome from cataract surgery or other causes – explant or implant? Difficulties arise when the IOL BVP required is outside the range offered by makers of so-called phakic IOLs, i.e. IOLs that are added to existing IOLs or those who are still phakic (often with high ametropias), to correct significant residual or induced errors when explantation is not an option or is rejected by an informed patient.

One of the go-to IOLs in such situations is the Rayner Sulcoflex, which is offered in the power range ±10 D. A competitor is the Staar ICL, which spans the range +10 to –18 D.

IOL explantation can be required if an IOL becomes subluxated or opacified, or if an uncorrectable refractive surprise is encountered. There are a number of techniques applicable, including IOL fragmentation with scissors, folding the lens in the anterior chamber before removal, or removal as a single piece through a necessarily large wound.

Other considerations of an explantation include the lengthy duration of the procedure, risk of zonular dehiscence, damage to the corneal endothelium, and its extended recovery time. Subsequent surgery can also result in a refractive surprise, because the important parameter of effective lens (IOL) position (ELP) can change as a result of the earlier explantation.

Bala expressed some hope that the nascent technology of adjustable-power IOLs will eventually deliver solutions for all but the most extreme refractive surprises.

A 2015 paper of which Bala was the lead author showed that it is feasible to use a femtosecond laser (FSL) in vitro to fragment an IOL (hydrophobic and hydrophilic) in preparation for explantation via a minimalist incision. That paper suggested in vivo animal studies were warranted to evolve the technique and assess the safety issues involved.

Several noxious chemical by-products’ of the process were identified in vitro (e.g. at 12 microJoules styrene, toluene, phenylethyne, and ethyl benzene, but at 1 microJoule no gases were detected) some depending on the chemistry of the IOL. They determined that the best setting was a 3-micron spot applied as a 6-micron deep layer at an energy level of 8 microJoules.

Bala’s frontier lecture concerned the Optiwave Refractive Analysis (ORA) system, an aberrometer-based optical device that verifies intraoperatively, the IOL power required in each eye after the crystalline lens has been removed and the eye re-inflated to normal dimensions (as confirmed by tonometry). The manufacturer claims that its system can be used on eyes that have already had refractive surgery or for which there is unreliable biometry.

The ORA system is mounted around the operating microscope’s objective lens. A comprehensive user interface gives constant feedback, including warnings to the surgeon, and accepts specific IOL designs by tradename and lens type. Error prediction is based on the surgeon’s own collected and collated (AnalyzOR) data and comparisons with analogous global data. Ultimately, local data becomes part of the global database. An audit of historic outcomes over a user-selectable time period is also offered.

Bala and colleagues undertook an analysis of their practice’s results from October 2016 to the present and found that in the case of the IOL decision, 39% of cases ORA confirmed their plans; in 42% of cases ORA influenced the decisions made subsequently; and in just 19% of cases, the original pre-op plans remained unchanged.

According to Bala, even when everything is in agreement, up to 40% of cases can still be ‘off target’ probably because of variation in the ELP parameter. He estimated that ORA was helpful in influencing the surgeons IOL choice in 95.7% of cases, largely because of the availability of the database.

His summary was that intraoperative aberrometry improved IOL selection in ‘at least’ 95% of cases, it highlighted the need to measure posterior corneal astigmatism rather than infer it, customisation is better than optimisation, and errors of 0.6 D or better were achieved in 95% of cases. He did reveal that ORA was better when dealing with spherical errors than astigmatic ones.

Tellingly, Bala also admitted that patient expectations had ‘tightened’ over the years and now a 6/9 result is regarded as a ‘fail’ whereas once it was considered a ‘good’ result.

Part two of Lewis Williams’ report will summarise presentations on AI and ophthalmology, the retina, and penetrating eye injuries.


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