m
Recent Posts
Connect with:
Tuesday / June 18.
HomemifeatureImproving Ophthalmology Outcomes for Patients at RPAH

Improving Ophthalmology Outcomes for Patients at RPAH

The Royal Prince Alfred Hospital (RPAH) in Sydney is one of Australia’s premier tertiary referral hospitals, the principal teaching hospital of the University of Sydney, and the flagship of the Sydney Local Health District.

As such, ophthalmologists here are working at the forefront of translational ophthalmic research. In this article, three ophthalmologists write about advances in the management of thyroid eye disease and retinal disease, as well as new technologies from Zeiss that are changing the way surgical decisions are made and implemented.

A Multidisciplinary Approach to Thyroid Eye Disease

Associate Professor Raf Ghabrial 

In a first-of-its-kind for Australia, RPAH, in conjunction with the University of Sydney, has established a multidisciplinary monthly bulk-billing clinic that is expected to improve outcomes for patients with thyroid eye disease (TED).

Figure 1. A patient one week after left
decompression surgery.

DEFINITION

TED is an autoimmune process which affects the tissues of the orbit behind the eye. This can cause disfiguring proptosis, diplopia, and can threaten sight via optic nerve compression, or exposure of the cornea.

PATHOLOGY

In essence, TED involves accumulation of tissue and fluid, which causes pressure on the orbital contents. TED is described as having an initial active phase, followed by an inactive phase. The active phase is characterised by inflammation and infiltration of orbital tissues by immune cells. Glycosaminoglycans are deposited, causing oedema. The extraocular muscles are the most frequently affected tissues, resulting in swelling and fibrosis.

CLINICAL PRESENTATION

The most frequent sign in TED is eyelid retraction (present in over 90% of patients). Patients may have visible oedema and erythema of the periorbital tissues. Proptosis and lid-lag are also common. Dysfunction of the extraocular muscles can lead to diplopia. Incomplete eyelid closure (lagophthalmos) may develop, and patients might complain of exposure symptoms (such as foreign body sensation). Swelling of muscles at the apex of the orbit can cause pressure on the optic nerve, leading to optic neuropathy. This is only seen in severe disease (5% of patients with TED).

INVESTIGATIONS

CT is the most common imaging modality for evaluating TED. Findings may include rectus muscle belly enlargement, an increase in orbital fat volume, and crowding of the optic nerve at the orbital apex.

TREATMENT

Treatments for TED aim to relieve symptoms, preserve and optimise vision, reduce inflammation, correct strabismus, and improve cosmetic appearance. Optimisation of the thyroid status is important, but does not alter the underlying pathology of thyroid eye disease.

Figure 2. Severe macula and retinal ischaemia.
Protocol W has shown regression of clinical diabetic retinopathy with regular Eylea. This study may also illuminate whether regular anti-VEGF slows retinal ischaemia on fluorescein angiography as well.

Generally, patients should be advised regarding the risks of smoking and the benefits of cessation. Symptomatic relief may be achieved by supportive measures, such as head elevation in sleep, ocular lubrication and sunglasses to reduce photophobia. More specific treatments depend on the activity and severity of the disease process.

In the active phase, the inflammatory process may be targeted by steroids and immunomodulatory agents, like cyclosporine or azathioprine. Radiotherapy has also been used to reduce inflammation. Recently, a monoclonal antibody to the insulin-like growth factor I receptor (IGF-IR) called teprotumumab was shown to be effective in treating active TED. Teprotumumab has been granted United States Food and Drug Administration approval but is not yet readily available in Australia.

The inactive phase is characterised by stable alterations in the orbital tissues. Treatments for this phase of the condition are primarily surgical, and are generally considered after stability for around six months. An important sequence of interventions should be followed, whereby decompression of the orbit is performed prior to extraocular muscle surgery, which in turn precedes eyelid surgery. This is because the former procedures will have a direct effect on the subsequent issues.

WHEN TO REFER

Referral to an ophthalmologist is encouraged for patients with ocular or cosmetic symptoms. Urgent referral is necessary in the presence of vision threatening disease.

Due to the complexity of management of these patients, and the tendency for their care to be delayed and fragmented, a multidisciplinary clinic has been established at RPAH in conjunction with the University of Sydney. This monthly bulk-billing clinic, fi rst-of-its-kind in Australia, involves specialists from ophthalmology (including orbital surgery, strabismus surgery, oculoplastics and ocular immunology) as well as endocrinology, radiology, and radiation oncology. At the time of writing this article, we are gathering data on the outcomes of the clinic for publication. We expect to show good outcomes for these patients who suffer from a condition that can have a profound effect on quality of life.

Advances in Treatments for the Macula and Retina

Dr Andrew Kaines

The two main diseases that affect the macula and retina are macular degeneration and diabetic retinopathy. At RPAH, our ophthalmologists are contributing to exciting advances in the treatment of both these conditions, as well as to the treatment of genetic eye disease.

Figure 3. iOCT image of vitreomacular traction.

AGE-RELATED MACULAR DEGENERATION

Faricimab for the treatment of neovascular age-related macular degeneration (n-AMD), has now completed phase 3 trials (TENAYA and LUCERNE). Faricimab is a bispecific antibody in that it targets both VEGF inhibition and is combined with an ANG 2 inhibitor. The ANG 2 inhibition reduces vascular leakage, stabilises vessels and reduces inflammation. The anti-VEGF component reduces vascular leakage and inhibits neovascularisation. Clinically, the main potential benefit for this medication is less frequent intravitreal injections – it is hoped that almost 80% of patients will be able to achieve 12 or 16-weekly injections while maintaining the same level of vision as previous agents. It is however, expected that the take-up of this new medication will be cautious as wider experience is developed with its side-effect profi le. Faricimab is also being investigated for diabetic macula oedema.

Figure 4. DMEK (Descemet Membrane Endothelial Keratoplasty) procedure. The iOCT image shows the curl of the donor membrane. Without iOCT it can be difficult to confirm the curl direction is correct.

There is also new treatment pending for dry (atrophic) age-related macular degeneration. Geographic atrophy (GA) has, up until now, only been treatable with conservative measures, like avoiding smoking, having a healthy diet, and taking an antioxidant vitamin such as MacuVision Plus or similar. Recent phase 3 trials (OAKS and DERBY) showed pegcetacoplan, given as intra-vitreal injections, can slow the progression of this atrophic change. For these trials, injections were given every month or every other month, making the treatment burden quite high for patients. As well as this, the treatment effect was modest, with a 10– 20% reduction in progression. In patients with extrafoveal GA, the reduction in the rate of progression was closer to 25%. It should also be noted that in the group receiving injections (compared to sham) there was an increased (approximately double) rate of neovascular AMD. However, having an active treatment available for the fi rst time is a major step forward. In selected patients, especially those with vision threatening atrophy, this may be of significant benefit.

DIABETIC RETINOPATHY

In diabetes, the two-year results of Protocol W have been released by the DRCR Retina Network. They gave patients with moderate-to-severe non-proliferative diabetic retinopathy (and absent macula oedema) a series of Eylea injections (or placebo). Currently, these patients are observed and encouraged to avoid smoking, optimise glycaemic levels (and atherosclerotic risk factors) and potentially take fenofibrate. In Protocol W, it was proposed that regular Eylea would reduce the rate of progression to either diabetic macula oedema (DMO) or proliferative diabetic retinopathy (PDR). If these two forms of advanced retinopathy could be prevented, then hopefully associated vision loss could also be reduced. The results showed a halving of PDR in the Eylea group, from 33% to 13%, and a three-fold reduction in DMO, from 15% to 4%. However, somewhat surprisingly, visual acuity was not improved. This is a four-year study, so later results will be very interesting. It has also shown many patients improved their NPDR grading of retinopathy, e.g. from severe to mild. However, up until now, no convincing evidence has shown anti-VEGF to either reverse or slow the progression of retinal ischaemia on fluorescein angiography. This trial will hopefully provide an answer to this as well. Lastly, although retinitis pigmentosa is a rare disease, a gene therapy treatment (Luxturna) has been approved for one genetic cause (RPE65) of this condition. This marks a major step forward for the treatment of retinitis pigmentosa and, more generally, genetic eye disease. We hope that other gene therapies will become available with time.

Microscope-integrated Intraoperative OCT in Ophthalmic Surgery

Dr James Leong

With the acquisition of the Zeiss OPMI Lumera 700 operating microscope, ophthalmic surgeons at RPAH now have access to intraoperative optical coherence tomography (iOCT) imaging through an integrated Rescan 700 OCT system. The emergence of microscope-integrated iOCT technology allows real-time OCT imaging during ophthalmic surgery. The spectral domain OCT images can be visualised through one of the surgeon’s oculars, superimposed with the standard surgical view. While this potentially provides real-time feedback during surgical manoeuvres, surgeons will often pause and refer to the assistance functions of Zeiss Callisto eye for larger, higher contrast and higher resolution images.

iOCT technology essentially provides an additional layer of information during surgery that is not evident with the standard surgical microscope. It has both anterior segment and vitreoretinal surgical applications, which have been evaluated in several prospective studies, the largest of which was the DISCOVER trial.1 In numerous surgical situations, iOCT imaging has been found to provide valuable input, which in some cases potentially guides surgical decision making.

Figure 5. iOCT is used in this glaucoma case to control the proper placement of a stent in tissue.

In anterior segment surgery, iOCT has been found to be particularly useful during corneal transplant procedures and glaucoma surgery. In lamellar corneal transplant surgery for example, the iOCT images assist in evaluation of graft host apposition as well as graft orientation. As would be expected, iOCT imaging of the angle is useful during glaucoma filtering procedures and minimally invasive glaucoma surgery (MIGS)/stent procedures.2

The technology has been applied to a wide variety of vitreoretinal disorders, particularly in vitreoretinal interface surgery such as epiretinal membrane (ERM) peels, vitreomacular traction and macular hole surgery. For example, during ERM surgery, iOCT can assist in determining preferred cleavage sites to initiate peeling and subsequently, reveal residual membranes. It can provide realtime assessment of vitreomacular traction (Figure 3) and the successful release of this traction. In retinal detachment surgery, iOCT can detect sub retinal fluid and in macula-splitting cases assess whether the fovea is involved. It is particularly useful in cases where media opacities, such as vitreous haemorrhage, have prevented preoperative OCT evaluation of the macula.

Finally, in the tertiary hospital setting, iOCT has a potential role in teaching and improving trainees’ understanding of surgical procedures. With further research and development, the utility of iOCT will continue to expand and we will likely continue to see advancements in image-guided ophthalmic surgery.

Assoc/Prof Raf Ghabrial is an ophthalmologist with fellowship qualifications from the United Kingdom and the United States in oculoplastic and orbital surgery. He consults publicly at RPAH and Sydney Eye Hospital. His private rooms are located in the CBD and Brookvale. 

Dr Andrew Kaines is an ophthalmologist with fellowship qualifications in medical retina from Moorfields Eye Hospital in London, and the Jules Stein Institute UCLA, in California. He consults publicly at RPAH. His private rooms are located at Brookvale, Blacktown and Eastwood. He also works for the Northern Beaches Hospital. 

Dr James Leong is an ophthalmologist with dual fellowship qualifications in vitreo-retinal surgery from the University of British Columbia, Vancouver Canada and in medical retina from Moorfields Eye Hospital, London. He consults publicly at RPAH, Sydney Eye Hospital and Concord Repatriation General Hospital. His private rooms are located at Liverpool, Strathfield, Illawarra, Miranda and Hurstville. 

References 

  1. Ehlers JP, Modi YS, Pecen PE, et al. The DISCOVER study 3-year results: feasibility and usefulness of microscope-integrated Intraoperative OCT during ophthalmic surgery. Ophthalmology. 2018;125(7): 1014-1027. 
  2. Ang BC, Lim SY and Doraira S. Intra-operative optical coherence tomography in glaucoma surgery – a systematic review. Eye(Lond). 2020 Jan;34(1):168–177.