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The Sydney Eye Hospital Alumni Association 12th biennial meeting

31/10/2018By Lewis Williams PhD
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Some of Australia’s leading ophthalmologists convened at Sydney Eye Hospital earlier this year for its Alumni Association’s 12th biennial meeting. LEWIS WILLIAMS distils some of the fascinating presentations made on the day.

The Sydney Eye Hospital (SEH) Alumni Association Biennial Meeting was held at the Sofitel Sydney Wentworth Hotel on July 28. As usual, the audience size was at the venue’s capacity.

SEH Alumni Association Chair Dr Ross Ferrier welcomed delegates to the packed 1-day program, which moved promptly to a first session consisting of numerous brief presentations based on grand rounds cases involving the presenter or presenters.

Grand rounds cases

Dr Kate Leahy gave the first presentation, which proved that unilateral, chronic, red eye is not always conjunctivitis – arguably a message for all eyecare practitioners and GPs alike.

Leahy’s other message was that an internal carotid-cavernous fistula (CCF) can have a subtle presentation, and not necessarily the manifestation recorded in texts, which describes the likely outcome as sudden engorgement of blood vessels and ocular hyperaemia on the ipsilateral side.

By far the most disturbing presentation of the day concerned a male model from India who rejected professional advice on numerous occasions concerning his implanted, light-coloured irides that were sending him blind. Perhaps with some deserved sarcasm, the presentation by Dr Yen Chen was titled ‘What Pretty Eyes’.

The implants were installed in India using a procedure and devices not approved for use in Australia. The initial presentation was for microcystic corneal oedema with an attendant reduction in vision. A slit-lamp examination revealed some cells in the anterior chamber (AC), a heavily pigmented trabecular meshwork, and the implant bearing on the angle (implant’s OD was too large). Anterior OCT confirmed that the edges of the implant impinged noticeably on the angle’s structure.

Despite the obvious professional advice and even after the prescribed medication’s maximum dosage had been reached, he still flatly refused increasingly stern advice to the effect that his implants had to be removed. To avoid professional care, he resorted to delaying or even not attending appointments knowing (correctly) what would transpire at such a consultation.

The literature already predicted that, even after explantation, it was highly likely (50% or more of cases) that he would require a 2nd round of surgery to settle the AC/anterior angle. Obviously, explantation requires AC re-entry but the implant’s opaque nature makes native iris visualisation impossible.

Furthermore, because the implant was now embedded in, and ‘expanding’ the anterior eye, extensive breaking of almost a full circle of adhesions was going to be required. Removal of such a large implant also required its surgical segmentation and maximum use of viscoelastic during the procedure.

According to Chen the implant was “impaled in the trabecular meshwork”. While the implant was still in situ, the IOP had been increasing and for a year at least, the model’s IOP was about 40 mm Hg which resulted in permanently reduced VA.

Eventually, his failing sight ‘won’ the day and the implants were removed.

KEYNOTE SPEAKERS

Ross Ferrier

Charles McGhee

John Hogden

Phillipa Sharwood

Stephanie Watson

John Grigg

Travelling scholarship

The most recent winner of the SEH Alumni Association’s Travelling Scholarship, Brisbane-based Dr John Hogden, detailed his experiences with the program.

Hogden travelled to the University of British Columbia (Vancouver, Canada), where Drs Simon Holland and Martin McCarthy mentored him. The fellowship program directed by Holland was responsible for five grafts a week, using procedures including penetrating keratoplasty, DMEK, DALK, DSAEK, and insertion of the Boston KPro (keratoprosthesis).

On his return to Australia, Hogden increased his usage of the DMEK procedure. However, he advised delegates to avoid DMEK in phakic eyes until they were experienced with the procedure and to avoid high myopia if at all possible.

By way of general advice based on his experience, for reasons of safety in use he recommended that 20% sulphur hexafluoride (SF6) gas be used whenever a gas tamponade was required. For keratoconus, he favoured topography-guided PRK along with CXL. His preferred excimer laser was the Schwind Amaris 1050RS (using a pulse rate of 1,050 Hz) along with its SmartSurfACE stromal surface-smoothing technology.

Donaldson lecture

The 2018 Donaldson Medal was awarded to the renowned academic, Professor Charles McGhee from the University of Auckland, where he is the foundation (1999) Professor and Chair of Ophthalmology.

A University of Glasgow graduate in medicine and science (1976–1983), he was an ophthalmology professor by 1996. McGhee ascended to the UAuck chair position just three years later – a position he still holds.

Unsurprisingly, his lecture topic was keratoconus (KC), a topic his name has long been synonymous with. One of his opening claims is that “as we approach the year 2020, keratoconus as a disease is in its twilight years”.

The aetiology of KC is considered to be multifactorial, there are genetic and environmental components, and there are probably different pathological processes involved. Prevalence can be anywhere between 8.8 and 54.4 cases per 100,000 people.

However, since the widespread introduction of topographers circa 1990, some authorities raised the likely prevalence to about 3.3% of the population.

The condition is believed to be dominant because, with the aid of topographers, it has been shown that more than 50% of blood relatives of KC cases exhibit corneal abnormalities and/or astigmatism, often irregular. For KC, McGhee finds the Orbscan topographer to be more useful although the Galilei (Zeimer) and Pentacam HR (Oculus) devices were also reviewed favourably.

Regardless of the device chosen or available, he recommended strongly that, because of differences between devices and their outputs, the same device be used in longitudinal studies if valid comparisons are to be made.

Histologically (and optically as a direct result), the irregularities found in Bowman’s layer are smoothed out/over by the overlying corneal epithelium, albeit with some local increases in corneal surface curvature.

Apart from the inheritance angle, KC also has several other genetic associations, e.g., the following syndromes: Down, Marfan, and Ehlers-Danlos, mitral valve prolapse (KC in more than 40% of cases), and Leber’s congenital amaurosis. Down syndrome in particular has a close association with KC, ranging from 10–38 cases out of 98, depending on the criteria used.

Genetic suspects identified to date include mutations in: VSX1, COL4A3, COL4A4, 2EB1, TGFß1, and SOD1. KC has been detected in patients as young as 8 years of age, but most cases commence around puberty. While most cases seem to stop progressing significantly around 40 years of age, to use McGhee’s claim, “KC never sleeps”, a claim confirmed by various NZ-based studies.

According to Aotearoa Research in Keratoconus (ARK) figures, around 20% of cases progress to a penetrating keratoplasty. A contributing factor to KC problems can be the presence of stromal fluid leading to corneal problems, a situation that develops usually within the 4 years following initial diagnosis.

About a third of ARK study patients made their first connection with either an ophthalmologist or an optometrist during the study. McGhee noted that previous episodes of hydrops predicts poorer disease outcomes, and that KC was not a central corneal disease – a recurrent ectasia in host tissue post-graft confirms that assertion. In fact, McGhee claimed that the condition was not ‘recurrent’ but rather ‘ongoing’ in reality.

KC involves microstructural changes, microtrauma, and micromolecular alterations of the cornea. He also suspects that apoptosis of keratocytes might also be implicated, and reported that there were cell density decreases in the basal epithelium, anterior and posterior keratocytes, and the corneal endothelium. There were also changes in the sub-basal nerve plexus.

McGhee’s conclusion was that KC was a disease of the whole cornea with grossly abnormal cellular morphology and decreased cell densities. Hydrops was described as, “a lot of inflammation and not just water imbibition”.

The related issues of atopy and eye rubbing in KC are now accepted and the avoidance of eye rubbing is a normal recommendation in KC discussions. The use of preservative-free topical anti-allergy eye drops help decrease the stimuli to rubbing eyes. It has been shown that the keratocytes in KC corneas have 4x the normal IL-1 (Interleukin-1) receptors.

McGhee believes that pellucid marginal degeneration is not different to KC, just a different location on the same spectrum. Despite the hopes of many researchers, corneal biomechanical studies have failed to reveal any new information to date.

KEYNOTE SPEAKERS

Peter McCluskey

Tess Huynh

Peter Sumich

The care of KC patients has evolved somewhat over the past decade or two, especially in the surgical options used to treat the abnormal cornea. Most still resort to rigid CL initially but NZ figures suggest that about 31% of cases proceed to a penetrating keratoplasty.

Partly because corneal grafts don’t last forever and therefore need to be repeated, NZ data from 1991–1999 showed that 45.6% of all grafts were in KC patients (initial and repeat keratoplasties). Described as the procedure du jour, DALK is the most common surgical approach, with CXL becoming increasingly common.

CXL tends to stop the progression of KC that also flattens the cornea somewhat. While McGhee believes that CXL is here to stay, a Cochrane review of the results suggests that 2 D corneal flattening and an improvement of between 2 and 10 letters in VA are what can be expected from the procedure. The review also noted that many trials were executed poorly and as a result the data was sub-optimal.

Despite the immune privilege given to the cornea because of its largely avascular anatomy, corneal graft failure rates can still be around one in three. Because of the retention of the host’s corneal endothelium, the rejection rates in DALK are lower. McGhee’s parting comment was that not all of KC’s secrets are known yet.

The SSI

Professor John Grigg reported that the SEH’s Save Sight Institute (SSI) is sixth ranked specialist eye hospital in the world. He gave an overview of the management of inherited eye disorders and the prospects for their treatment.

Factors to be considered include: the diagnosis (ophthalmic and genetic), the disease’s natural history (imaging, studies of function, patient-reported outcomes), therapies (gene replacement, gene edits, stem cell therapies), optogenetics, vision and education support, the NDIS, and considerations of the health economics involved.

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Additionally, the suitability to entry in an SSI registry to track the case and contribute to knowledge was also a consideration. He claimed that Australia was good at translating genetic information to patient management.

Grigg went on to detail the cost of one novel intervention involving the enzyme RPE65 – a cost of $1 million to the patient for a one-off treatment. Genetic studies confirm the variance within a particular disease and investigations are required to ascertain whether it’s the core disease or a variant of it that’s causing the manifest disease under investigation.

SSI’s Professor Peter McCluskey detailed a new model of care for those suffering from uveitis and rheumatoid arthritis when he spoke about the combined paediatric uveitis and rheumatology multidisciplinary clinic at SEH. The association between uveitis and other systemic diseases, such as JIA, as well as related problems of CMO, cataract, and ocular hypertension/glaucoma, motivated the idea behind a ‘one-stop shop’ approach to the problems involved.

The clinic follows EULAR 2018 Guidelines (European League Against Rheumatism). Ophthalmology and paediatric rheumatology have been working together since October 2015 and the SSI/SEH multidisciplinary team dealing with paediatric uveitis is now seeing around 16 patients per month. To complicate matters, up to 40% of cases also prove to be steroid responders.

If active uveitis is discovered in a JIA case, McCluskey advised the audience to treat immediately. An 87% reduction in the risk of secondary cataract can be achieved if the dosage rate can be held to fewer than 3 steroid drops per day. If that’s not possible, he suggested a systemic medication approach instead.

Methotrexate was the first choice for systemic immunosuppression. If the condition is still uncontrolled, he suggested a switch to a biologic alternative, e.g., adalimumab, which has a lower relapse rate than methotrexate. The multidisciplinary clinic has seen individual patient visits drop from 3–5 consultations per month to an extended single visit in most cases.

Dr Tess Huynh discussed aspects of improving cataract surgery outcomes, noting the increasing expectations that have occurred over the last 40+ years. She reported that the top 1% of cataract and refractive surgeons can now achieve ±0.50 D outcomes, 90% of the time.

Error sources in descending order of significance are: IOL position, IOL Rx (BVP), eye axial length (AL), and pupil position. An error of 0.3 mm in AL approximates to a 1 D mistake, and when estimating AL in a densely cataractous patient, swept source OCT is superior.

Huynh also suggested that if suboptimal, the ocular surface should be improved before cataract surgery. Should post-surgical astigmatism be ≥3 D, Huynh suggested that Kerarings, usually with CXL, be considered as a possible answer.

Australian Society of Ophthalmologists president Dr Peter Sumich tackled the thorny issue of refractive surprises after cataract surgery. Causes range from gross errors such as implanting the wrong IOL (an old issue well managed by suitable theatre procedures and cross/double checking), errors in biometry (a decreasing problem as instrument sophistication improves), and errors in estimating the effective IOL position within the eye.

He attributed fault to the surgeon if they plan poorly, fail to listen to the patient’s history, vision needs, etc., and don’t account for the fact that many myopes remove their specs for near, something that is pointless after cataract surgery.

He described Rayner’s Sulcoflex IOL as a surgeon’s best friend in cases of refractive surprise and went on to suggest other possibilities such as laser refractive surgery, toric IOL realignment and, in a worst-case scenario, explantation of the IOL.

Sumich described the Sulcoflex lens as being easy and safe to use. OCT can be used to assess the anterior segment prior to implantation, no peripheral iridectomy(ies) is/are required, and Rxs in the range ±5 D were available.

He suggested avoiding the addition of a toric IOL in surprise cases as they can rotate, complicating the situation further. He also advised the use of the IOL manufacturer’s calculator to resolve refractive issues and, if in doubt, lean towards a myopic outcome.

If a laser solution has been decided upon, i.e., LASIK or PRK, he noted that myopic LASIK was ‘easier’. If a toric IOL realignment would solve a refractive problem, Sumich suggested that it be done early, certainly before any IOL ‘incorporation’ into the anterior chamber occurred, because it’s easy to do.

However, contrary to the views of some surgeons, he recommended against IOL rotation being carried out at a slit-lamp. He reported that small eyes and IOLs with high BVPs are trickier to rotate the amount required. For eyes that are post-LASIK, he recommended the use of the ASCRS calculator.

Other difficult cases he identified included: the elderly with PXF, cases with poor biometry/keratometry results, anisometropes, and non-English speakers or those whose native tongue is different from that of the surgeon.

Management of patient expectations is ‘everything’ according to Sumich. Use of couched words such as ‘estimate’ should be used instead of making claims or promises that might not be realised.

He recommended spending 5 minutes pre-operatively to discuss likely outcomes and to weave into the conversation that, “You’ll be buying glasses again for something, at some time in the future”, to avoid suggestions that they will be glasses-free once the eyes settle down after surgery.

A demonstration of likely outcomes using a trial frame or CLs was also suggested. He described accidental hyperopia as ‘irrecoverable’. To the less experienced surgeons in the audience he recommended they avoid multifocal IOLs until they were up to speed and his parting comment was that the J&J TECNIS Symfony IOL was “very forgiving”.

Summary

What became obvious over the day’s program were the often difficult situations that confront ophthalmologists working in a tertiary referral centre such as SEH.

Frequently, especially in cases where co-morbidities exist and/or the patient is under the care of multiple specialists for multiple conditions that may or may not be related to one another, what the ophthalmologist would do normally might be countered by factors relating to a co-morbidity or blocked by another specialist – sometimes for life-threatening reasons.

The lateral thinking, the forced decisions, the risks, etc. that are needed would tax the best minds but if you are in the driver’s seat, the decision can often rest with you, possibly with learned input from colleagues. In some cases, the patient ends up at SEH because their original consultant has determined that the care or equipment required is beyond them or their resources.

The SEH consultants, and their registrar understudies, are then confronted by challenges that must, at times, seem daunting if not insurmountable. Without those ‘wicket-keepers’, eyecare would be inferior to what is on offer currently.

Corneal issues

Dr Matt Ball delivered a presentation titled ‘The cornea – window to the body’. His theme was dysbiosis (in his introduction he targeted abnormal gut flora specifically) and its links to diseases such as MS, Sjögren’s syndrome, uveitis, CNV, mucous membrane diseases, and possibly dry eye.

The long-established link between vitamin deficiency (A, B, and C appear in the literature) and corneal transparency were mentioned in his introduction. The 16S rRNA of bacteria in a microbiome can be used as a barcode (gene sequencing) to identify the bacteria present.

When the normal human microbiome is compared with that of a Sjögren’s case for example, the latter was shown to lack biodiversity, the firmicutes to bacteroidetes ratio was increased, and there was evidence of a lack of immune cell regulation. Endotoxins are able to pass through the gut wall and inflammation can result.

Dysbiosis decreases both organism diversity and the beneficial organisms present. Ball noted that the concept that ‘food is medicine’ is not new and was noted by Hippocrates (460–370 BC) a long time ago. While probiotics were of unknown efficacy and very recent studies have suggested they are useless or even harmful, Ball saw a possible role for prebiotics, i.e., food selected to target specific (beneficial) organisms.

Professor Stephanie Watson talked about corneal infection from a SEH perspective, where it is considered an ongoing and significant issue. Microbial keratitis is sight-threatening and when it occurs in the eye of an elderly person about 10% of cases will lose an eye.

Corneal scrapes show that about 75% of cases are due to a Gram +ve micro-organism, about 21% are due to Gram –ve organisms, and about 4% are fungal in origin. Few cases were caused by Acanthamoeba spp. Resistance to existing antimicrobials is such a problem worldwide that the WHO has launched campaigns to combat it lest we return to the pre-antibiotic era, where there was little the medical profession could do other than to support the body’s own defence mechanisms.

Watson admits that the SEH has a resistance problem, often due to patient non-compliance, such as failing to complete a full course of antibiotics, which leads to the survival of the most resistant organisms thereby refining a resistant species.

To study the problem in-depth, the SEH has launched KARSP (Keratitis Antimicrobial Resistance Surveillance Program). An ‘antibiogram’ is a feature of KARSP in which the number of cases assayed and the number resistant is recorded.

She also noted that a common antibiotic, ciprofloxacin, can result in white corneal deposits with extended use, and that now that chloramphenicol is available OTC, its use has increased significantly. Unfortunately, it’s ineffective or inadequately effective against Pseudomonas aeruginosa, a common ocular pathogen.

As a result, loss of vision or even eyes has occurred due to effective treatment being delayed while self-medication was pursued. RANZCO is in the process of creating guidelines for chloramphenicol usage for GPs, optometrists, and pharmacists to reduce the likelihood of further losses.

According to Watson, outcomes can be improved by identifying the organism promptly, initiating the best therapy, educate the public (before an infection) and patients (after infection), and to improve the overall patient experience should they become infected.

SEH Alumni Association Scholarship 2015 winner and paediatric ophthalmologist ß, now located at the Lady Cilento Children’s Hospital in Brisbane, gave a brief overview of her time in the UK. Sharwood spent time in specialist children’s hospitals, such as Great Ormond Street (London Hospital for Sick Children, Bloomsbury) and Addensbrooke’s (Cambridge University Children’s Hospital).

Her main exposure was to cases involving the cornea, cataract, glaucoma, neuro-ophthalmology, retina, uveitis, CMO, and problems of the adnexa. Overlapping one or more of those areas were the many genetic eye problems represented in children’s eye diseases.

Sharwood noted that although paediatric uveitis was rare, it was also potentially blinding. About 50% of childhood uveitis is associated with JIA (Juvenile Idiopathic Arthritis) and about 70% of those cases involve the anterior segment only.

IOLs were implanted in cases of uveitis-related cataract. She described management as difficult because the patient can relapse, can be asymptomatic at times, and can become amblyopic. She also reported a high rate of steroid-related ocular hypertension, something that is more likely to occur in young patients.

Newer treatments for RA, JIA, etc. such as adalimumab (Humira) and infliximab (Remicade and other names) were described as successful treatments (they are anti-TNF drugs). While difficult, intraocular surgery is sometimes essential in children within the amblyopic-age group.

While IOLs were once frowned upon in children, now it’s believed that as long as the eye is quiet for at least 3 months (6 months preferred), IOLs can be implanted in some cases.

Inflammation, another difficulty, was described as a time bomb. If IOLs are used, suppression of inflammation might also be required, but amblyopia remains a risk. Other complications include the IOLs being enveloped in a membrane and CMO.

About 75% of cases are put on steroid therapy, 70% of whom are on methotrexate. When multiple procedures are performed out of necessity, there is an increased risk of a poorer outcome. Up to 10% of cases experience a retinal detachment post-surgically.

Interestingly, having glaucoma was not a risk factor for a poorer visual outcome and ultimately, good VA was achieved in most cases. Some cases require IOL explantation or even develop phthisis bulbi.

 

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