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September 2010

Following the release of our September issue, here is the latest from Eye on Ophthalmology, In Contact and Point of View.

If you wish to comment on this column or are interested in subscribing email your details to info@nzoptics.co.nz

Happy Reading
Kind regards
The team at NZ Optics 

Eye on Ophthalmology

VEGF inhibitors and wet age related macular degeneration - the story so far

By: Dr David Squirrell*

Ocular angiogenesis, and choroidal neovascularisation in particular, remains the leading cause of blindness in New Zealanders over the age of 50 1. We have for a long time recognised that the principle driver of ocular angiogensesis is vascular endothelial growth factor (VEGF) and the arrival of the VEGF inhibitors ranibizumab and bevacizumab have transformed the management and outlook of many conditions that were, in the past, considered largely untreatable. In this article I will briefly summarise the pathophysiology of ocular angiogenesis and VEGF in particular before moving on to review the current data on the use of the VEGF inhibitors in wet Age related macular degeneration.

Figure 1. Active CNVM as demonstrated by dye leakage on Fluorescein angiography

Figure 2. Subretinal fluid is clearly seen indicating that the leison is active

Figure 3. The presence of new haemorrhage in a patient undergoing treatment for wet AMD is an indicator for further treatment with or without subretinal fluid or intraretinal oedema on OCT

Retinal and choroidal angiogenesis
Angiogensesis is a tightly controlled multistep process that is governed by a dynamic balance between positive and negative regulators. In health a delicate balance between these opposing stimuli is maintained which serves to regulate the retinal and choroidal circulations and negligible endothelial cell proliferation occurs. Angiogenesis itself is a complex process characterised by a cascade of events: initial vasodilatation of existing vessels is accompanied by increased vascular permeability and degradation of the surrounding matrix 2,3. This in turn allows activated and proliferating endothelial cells to migrate and form tubes. Subsequently a phase of maturation and remodelling of these new vessels takes place which ultimately forms a fibrovascular network. The principle stimulus for angiogenesis is ischaemia which in turn leads to an upregulation of a number of growth factors, integrins and proteinases. In the face of ongoing retinal and or choroidal ischaemia the process proceeds remorselessly to retinal or choroidal neovascularisation and ultimately to fibrosis, outer retinal atrophy and loss of function.

Although there were a myriad of potential candidates, VEGF-A emerged as the prime regulator of angiogenesis 3. It was found to both promote new vessel formation and increase the vascular permeability of existing and proliferating vessels. As a result VEGF-A was identified as a potential therapeutic target for suppressing ocular angiogenesis. In the human, four different VEGF –A isoforms have been identified each with varying lengths of amino acids: VEGF121, VEGF165, VEGF189, VEGF206. The longer forms of VEGF-A are matrix bound, the shorter forms are freely diffusible within the extracellular matrix and vitreous. From the perspective of therapeutic targets the presence of these different isoforms posed a very important question; namely as VEGF is important not only in driving neovascularisation but also in maintaining the healthy circulation should the therapeutic target be directed at one, the most prevalent, of these isoforms (VEGF165) or should it be directed at blocking all four isoforms. Two drug companies lined up on either side of this argument: Pfzier went for selective VEGF blockade with Macugen; Genetech and Novartis went for pan VEGF blockade with ranibizumab. Despite initial reservations that pan VEGF-A blockade would be detrimental and not tolerated ranibuzimab eventually ran out the clear winner. The VEGF-A molecule is however not the only potential therapeutic target for turning off ocular angiogenesis. If VEGF-A is to exert a biological action it must first bind to a receptor. Once bound it then has to initiate a transduction signal within the target cell. This in turn causes the expression of particular proteins which then influence the cell and its surrounding milieu. Future therapeutic strategies to inhibit ocular angiogenesis include targeting (blocking) the VEGF receptor and the intracellular transduction signal. Work is therefore ongoing to develop therapeutic targets to all these steps.

Ranibizumab (lucentis) or bevacizumab (avastin). What is the difference?
Whilst Genetech and Novartis ran out clear winners in the production of a commercially successful anti VEGF molecule, the development of their favoured molecule was not without its own controversy. Genetech had already developed a monoclonal antibody against all VEGF –A isoforms, namely bevacizumab. However after preliminary work on primates it was considered unsuitable for use in the human eye and a humanised molecule comprising a fragment of the original antibody was developed. This drug emerged as ranibuzimab. However whilst the original phase I and II trials of ranibuzimab were underway a small case series was published in which the authors demonstrated the effectiveness of systemic bevacizumab in patients with neovascular AMD. Whilst many in the ophthalmic community either ignored or overlooked this original paper it prompted the lead investigator of this paper to ask whether intravitreal bevacizumab would also work. The answer, published as an isolated case report in an obscure journal was "yes". Avastin (bevacizumab) had arrived. Whilst ranibizumab had undergone extensive safety testing as well as robust and expensive clinical trials to prove its worth the rapid uptake of bevacizumab into clinical practice soon produced a stream of uncontrolled case reports suggesting that at the very worst the results obtained with bevacizumab were not that inferior. Although bevacizumab and ranibuzimab are both pan VEGF-A blockers one has to remember that they are not identical molecules. The question as to whether they are equally effective remains unanswered but there are now at least 4 large head to head clinical trials of ranibizumab versus bevacizumab that are currently being run to answer this question the first of which should start to report late in 2011. However, from a health economics point of view, with ranibizumab costing approximately $2000 an injection and bevacizumab costing just $100 an injection, it has been estimated that ranibizumab would have to be 5 times more efficacious to be equally cost effective 4.

Anti VEGF agents and wet age related macular degeneration.
The Novartis sponsored landmark clinical trials, ANCHOR and MARINA clearly demonstrated that monthly administration of Ranibizumab not only halted the remorseless visual decline associated with active neovascular AMD from all lesion types but it actually lead to a dramatic improvement in visual function that was maintained into year 2 of treatment. With time the concept of "active neovascular" AMD has become central to the successful management of patients with wet AMD as the anti VEGF agents specifically target active angiogenesis and vascular permeability 5. The generally accepted criterion for active neovascular AMD are:

1. Abnormal retinal thickness, particularly with evidence of subretinal, intraretinal or sub pigment epithelial fluid accumulation as confirmed ideally on OCT.
2. Presence (or recurrence) of intraretinal or subretinal haemorrhage.
3. Persistent leakage as shown on FFA.
4. CNVM enlargement on FFA, unless due solely to fibrosis.
5. Deteriorating visual acuity.

The presence or otherwise of these features has evolved to guide both the initiation and maintenance of therapy. Once a patient is diagnosed with active neovascular AMD most physicians would initiate treatment with a loading regimen of 3 treatments given 1 month apart. However once treatment has been initiated two questions have to be asked. Firstly how frequently should patients be reviewed after treatment has been initiated? Secondly if an antiVEGF therapy is given in combination with another treatment (PDT or steroids) can we improve the visual acuity results or at the very least reduce the frequency of re treatments? Despite a plethora of different combination treatment regimens and variable dosing regimens the bottom line is no study has yet equalled the results obtained with regular monthly treatment 4. However, whilst regular monthly treatment (whether the lesion is active or not) is associated with the most favourable outcomes, this is impractical for most health economies and as a result different "disease sensitive" dosing regimens have emerged 6. The most common dosing regimen employed is the "prn" [PrONTo] regimen 7. The theory is simple. Review the all patient every 4 weeks. If the disease is "active" treat, if "inactive" withhold treatment and review again in 4 weeks. Although the simplicity of the regimen is attractive the Achilles heel of this regimen is being able to accurately identify an active lesion. This in turn is dependent upon principally how good your OCT is. If you OCT is of poor resolution you risk missing subtle active disease with its attendant risk of undetected disease progression. Another regimen which has found favour is the "treat and extend" regimen 8. In essence, you assess your patient and treat at every visit. If the lesion is active treat and review in 4 weeks, if inactive treat and review in time intervals that are slowly extended from 6 then 8 and finally 12 weeks. In practice most Ophthalmologists will follow their own favoured protocol which borrows from both these strategies but one rule of thumb which is increasingly being recognised is "if in doubt", treat.

Whilst it is often a reasonably easy decision to start treatment the question of when treatment should be discontinued is often one which is vexed and laden with much emotional overlay. There is now a consensus of opinion that treatment becomes futile when there is "established structural damage to the central fovea" 9. What this actually means in practice is rather flexible and the decision to discontinue treatment is one that has to be made after careful consultation with the patient. One can occasionally find oneself still treating a patient with a visual acuity of "CF" who is adamant that treatment helps, but most patients by this stage have accepted that further treatment makes little difference and are therefore happy for treatment to be discontinued. As with the management of patients with any chronic clinical condition the key to success is carefully managing the patients' anxieties, expectations and coping strategies. Finally, enrolling the support of allied professionals including optometrists (when can I go for new glasses doctor?) , the low vision services (for advice on contrast, glare, lighting as well as magnification) as well as organisations such as Macular Degeneration NZ, Retina New Zealand and the RNZFB is often essential if the patient and their families are to optimally supported.

References

1. The economic impact of vision loss in New Zealand 2009. Report by access economics pty limited for Vision 2020 New Zealand. July 2010.
2. Vascular endothelial growth factor; basic science and clinical progress. Ferrara N. Endocrine reviews 2004. 25: 581-611.
3. Retinal and choroidal angiogenesis; pathophysiology and strategies for inhibition. Das A, McGuire PG. Progress in retinal and eye research 2003; 22: 721-748.
4. Rosenfeld PJ. Intravitreal avastin: the low cost alternative to lucentis? Am J Ophthalmol 2006; 142: 1-9.
5. Ranibizumab (lucentis) in neovascular age-related macular degeneration: evidence from clinical trials. P Mitchel etal British journal of Ophthalmology 2010; 94: 2-13.
6. Spaide RF The as-needed treatment strategy for choroidal neovascularization: a feedback-based treatment system. Am J Ophthalmol. 2009 Jul; 148(1):1-3
7. Lalwani GA, Rosenfeld PJ, Fung AE et al. A variable dosing regimen with intravitreal ranibizumab for neovascular age related macular degeneration: year 2 of the PrONTO study. Am J Ophthalmol 2009; 148: 43-58.
8. A Treat and Extend Regimen Using Ranibizumab for Neovascular Age-Related Macular Degeneration Clinical and Economic Impact. Gupta OP, Shienbaum G, Patel AH, Fecarotta C, Kaiser RS, Regillo CD.Ophthalmology. 2010 Jun 29. [Epub ahead of print]
9. Royal College of Ophthalmologists Age related macular degeneration guidelines for management February 2009. available at http://www.rcophth.ac.uk/about/publications accessed August 2010

About the Author
* David initially served as an Officer in the Royal Navy before changing tack and electing to study medicine. He did his postgraduate ophthalmology training in South Yorkshire (UK) rounding off his training with medical retinal Fellowships in Auckland and the UK. After completing these fellowships David worked for 3 years as an NHS consultant back in Sheffield where he was instrumental in setting up one of the largest rapid access wet AMD services in England. Throughout his career he has always actively participated in research and now has over 20 peer reviewed papers to his name, most in the field of medical retina and ocular imaging. He was tempted back to Auckland last year and he now holds an appointment at Greenlane clinical centre where he works as a Specialist in Medical retina.

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In Contact

As You Do

As so often happens, the first patient I saw on return from Snowvision was the sort of case we discussed in our CPD sessions in Queenstown. Considering the après ski revelry I was impressed that I absorbed it and didn’t fall asleep.

I’d had an early morning cancellation on returning to work that Monday which was promptly filled with two red eye patients.

The first, new to our practice, was a thirty-five year old female legal executive, who’d developed a red eye five days prior. A pharmacist had provided Brolene eye drops for ‘conjunctivitis’ with no improvement. Over the weekend her eye had become painful and photophobic. The eye was watery with no mucous discharge. She had severe redness and conjunctival chemosis. The cornea was clear with no conjunctival staining. The pupil on the affected eye was constricted and there were trace cells in the anterior chamber with trace pigment on the lens. I diagnosed suspected iritis and referred her to an ophthalmologist. Two days later a report arrived confirming possible iritis with Rx Maxitrol. Based on opinions espoused by some lecturers, Maxitrol was arguably not the ‘best’ drop for such a case. With the conjunctiva looking as it did it was probably prescribed as a ‘cover’, albeit not the ‘ideal’ antibiotic. Some would say that maybe Maxidex or Pred Forte combined with a more targeted separate antibiotic eye drop would have been ideal. A swab and culture could help target the bugs if any were present, although potentially delay treatment.

The next ‘red eye’ was a thirteen year old schoolgirl who’d been fitted by a colleague with overnight Ortho-K a year ago  Her concerned parents had brought her in two weeks prior with a mild red eye, that seemed more related to meibomian gland dysfunction. I’d noted mild blepharitic ‘scaling’ of her distichiatic lashes and advised SteriLid for lid hygiene coupled with lid- massage. They requested the second visit as there was now mild discharge in the morning. They’d attended Greenlane Clinical Centre on the Sunday prior. The registrar suggested it might be a ‘mild virus’ and suggested no CLs for two weeks, although she’d already been off CLs for almost that time.

Discussion revealed she also had mild itching and had been sneezing of late.

She could be one of the rare people with SteriLid sensitivity so we suggested stopping that for a few days with a diagnostic trial of Livostin as the tarsal conjunctiva also showed some mild changes.

A review by my colleague two days later confirmed that things had settled and the Livostin had worked well. The only sign now was of a resolving tarsal conjunctiva and she will resume her OK lens wear. They took the opportunity to obtain an up to date backup pair of spectacles as they were off to Europe for a family holiday and wanted peace of mind while away.

Self Selection

So that was my welcome back to work after the conference. The rest of that day and week was chokka with the usual mix of cones, presbyopes and challenging cases. A long term presbyopic PRK patient wanted monovision as she’d developed some myopic ‘progression’. It worked a treat.

Another patient had self prescribed a +2.75 1 Day Acuvue Moist (that her friend had provided in the UK) but wanted professional fitting and management. I upgraded her into TruEye and she was immediately a great success. By pure chance her friend’s Rx was spot on!

Practising in the Auckland CBD for well over the past decade I have watched with interest the shift in demographics and change in our typical, traditional patient.  There has been a significant shift in our practice and in those shopping and walking around the city. We now, on an almost daily basis, have patients coming in from the Middle East and a variety of Asian countries almost demanding we sell them coloured lenses or the risk-laden ‘big eye’ circle lenses that Lady Gaga made famous. There are also all manner of requests for instant supply of Rx lenses from a variety of travellers from all over the world. They stay in the local backpackers and often just ask for ‘minus four’ or ‘four hundred degrees’ but have no idea of the brand or base curve. They don’t have prescriptions and if we do sight a foil pack it is often a rebranded lens making things even more difficult. They also want the lenses now as their bus is leaving for Rotorua later that day. Their cavalier attitude toward eye health and lens wear is both frightening and astounding. Their lack of preparedness also leaves us scratching our heads. They decline an eye exam and tell us they want lenses over the counter ‘just like they get in their home country’.

Sorry but we just don’t do it that way!

We do our best to help them out and would rather they have clean fresh lenses than wear a three month old, two-week disposable that they spit on to clean.

We are sitting on a time bomb of MK and other complications when one considers the increasing numbers of self prescribed lenses and modalities. Non-compliance rates as high as 80% and more are reported.

I have even seen a few people that had purchased extended wear silicone hydrogels online, having never been fitted with them, or been prescribed such lenses or modality. They simply buy them off the Net and start sleeping in them.

I hope that one day when the wheels fall off or their eyes fall out that they sue the hell out of the online suppliers who supply them without verifying the Rx. The manufacturers should not supply websites that provide lenses without Rx verification. The cynical among us would say they don’t care so long as they sell lenses, however the truth is that practitioners are going to prescribe less lenses if they see too many problems, so overall prescribing rates will drop. The low penetration of lenses is already a concern so maybe the manufacturers will wake up to these issues sometime?

In some cases it seems that patients have even been recommended such things by online suppliers. There appears to be some patient initiated switching of lens brands, with ‘generic recommendations’ of lenses and lens care solutions also suggested by the supplying websites.

If things do go wrong then this excellent freely downloadable Corneal Atlas from Review of Optometry is a must have. Excellent images with diagnostic  and  therapeutic management tips from renowned experts.

Nice.

Straight Facts?

I also note one of the retail optical chains is offering a ‘free 30 day supply of daily disposable silicon (sic) hydrogels’ with a spectacle package.

Is it a silly con or do they just not know the difference between silicon and silicone? Even Wikipedia clearly states that silicon should not be confused with the synthetic polymer silicone.

I hope they know the difference between the cornea and retina.

Don’t they check terminology and proof read the advertising?

One doesn’t know if these lenses are even fitted or trialed and whether their suitability is investigated prior to handing out the free supply of lenses, to ‘the same prescription’ as their glasses. One wonders if they even bother to vertex correct the Rx which in a -9.00D myope could make quite a difference. (At a vertex distance of 13mm this would equate to -8.00D at the corneal plane). A forty year old would not be too happy being over-corrected by a dioptre! I have also been told that the deal is dependent on signing up for ongoing supplies but people who’ve tried to obtain specific details have been left waiting for answers.

I wonder in how many cases less than optimal results will occur and in fact I wouldn’t be surprised if we see a few serious complications. We’ve already had some clients requesting less expensive lenses than the rebranded version they offer. The original lens is no longer independently available in our market as a result of a deal that alienated many ANZ practitioners.

It seems that their monopoly on these lenses is not exactly leading to the ‘best price’ either.

Funny that.

Some consumers are fortunately getting savvy and waking up to the fact that the big marketing machine is just that.

I cannot believe that the registered practitioners in such operations allow the marketeers to run roughshod over their professional ethics in such a way. Don’t the ECPs have the balls to stand up and tell them it’s not the way to do things? They should because at the end of the day it’s the optometrists’ butt on the line when things go wrong. They are the ones likely to be hammered and have their board registration cancelled and their livelihood terminated. If one reads the latest proposals by the Board to alter CPD and include things like ethical competence and so on then it is clear that practitioners need to stand their ground on such things. Not that it ever was any different as far as ethics are concerned. (See article on intended CPD changes elsewhere in this edition of NZ Optics and remember to submit your views on time!)

Optometry sure has been dumbed down and commercialised.

It’s just not the same is it?

More is the pity.

Coversely

At the same time I have also been surprised by the number of new patients I am seeing while retaining the bulk of my long term patients. We are also happy to have those that strayed return to us as they realise that you get what you pay for. This satisfactory patient load is especially positive when one considers we are probably lingering around at the bottom of a recession, as opposed to those who thought we were out of it and in recovery phase. One only needs to look at the numbers of liquidations and mortgagee sales, with shops closing all over the place, empty stores and sales of 30-70% almost everywhere you go.

Who would have guessed, a few years ago, that our largest optical wholesaler would be in receivership?

NZ Rulez

I noted with interest that NZ is now the largest per capita prescriber of si-hy lenses for daily wear and we beat Aussie, the home of si-hy lenses, by a good 10%. Check out some interesting results in the latest 2010 prescribing trends from Morgan et al. Here’s a link to a good summary.

If we could become the top single use prescribers on the planet I’d be way impressed.

NZ Rulez Reprise

The ABs deservedly took the Tri Nations in front of a record 95,000 people at the Calabash in SOWETO.

I’ll leave it to Buck Shelford to sum it up.

I couldn’t have said it better.

Epic

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Point of View

Ambliopia

By: Nicola Anstice & Rasha Al-Taie*

Case History

A 7-year-old girl was referred by her optometrist to the department of ophthalmology for assessment due to reduced vision in her left eye. She had been wearing glasses full-time for at least two years with a prescription of: RE (right eye) +0.50 giving VA (visual acuity) of 6/6, and LE (left eye) +3.50/-1.00x15 giving VA of 6/12-2

The patient’s first presentation to the department had occurred after failing her vision-screening test at the age of three years. Measurement of visual acuity at her first specialist appointment in July 2006 was 6/6 OD, 6/36 OS, no strabismus at distance or near was detected on cover test and gross stereopsis of 200” of arc (Lang stereotest) was measured. She was born at term and weighed 3080g at birth. Family history was notable for having an older brother with strabismus who had undergone patching. The rest of the medical history was unremarkable. Cycloplegic refraction was +1.50 RE, +4.50 LE and a diagnosis of anisometropic amblyopia was made. A spectacle prescription of plano RE, +3.00 LE was prescribed for full-time wear. She was then discharged due to failure to attend repeated follow-up visits and was re-referred by her optometrist in 2007 for another assessment due to failure to comply with the original treatment plan; re-assessment confirmed the original refraction and glasses were re-prescribed. Her care was transferred to her community optometrist due to repeated non-attendances to clinic and she was next seen in April 2010.

Vision with her current glasses was measured 6/6-1 RE and 6/15 LE, there was no strabismus on cover test and stereopsis was measured as 85” of arc as measured by Frisby stereotest. Cycloplegic refraction was: +1.75 RE, +4.50/-0.75 x 11 LE. It was recommended that she continue with the glasses, and occlusion therapy of the right eye was prescribed. The benefits and risks of both conventional patching and atropine penalization were discussed with the parents; due to shared parental custody and previous compliance issues, weekend atropine was commenced (atropine 1% RE once a week). At her first follow-up 6 weeks later visit visual acuity was 6/6-2 RE and had improved to 6/9.5-1 LE.

Optometry View – Nicola Anstice

Amblyopia is defined as visual loss in the absence of ocular pathology and is due to the abnormal development of visual brain areas caused by deficient visual stimulation. The most common causes of amblyopia are strabismus (38%) and anisometropia (35%), with less common causes being astigmatism, bilateral high ametropia, or stimulus deprivation. Amblyopia is the most common cause of monocular vision impairment in children with a prevalence of 2-5%. The lifetime risk of significant visual loss for the individual with significant amblyopia is substantial, being at least 1.2-3.3%.

The diagnosis of amblyopia requires the detection of a difference in visual acuity while wearing the appropriate spectacle correction. Therefore, both accurate measurement of visual acuity and performing a cycloplegic refraction on all children suspected of having amblyopia is mandatory. Improvement in visual acuity is the mainstay of monitoring the efficacy of amblyopia therapy, but a number of vision tests designed for use in children tend to over-estimate the visual acuity in amblyopic patients. Matching tasks (either letters or picture optotypes) have a high level of testability in younger children and the incorporation of ‘crowding bars’ to provide contour interaction improve the ability to detect visual loss due to amblyopia.

Potential treatments for amblyopia are limited, and the mainstay of treatment for more than 250 years has been the occlusion of the better eye, with either patching or pharmacological penalization, to promote visual function in the amblyopic eye. Until recently most published studies on amblyopia therapy have been retrospective reviews and therapeutic regimens have lacked standardization ranging from patching for minutes a day to all waking hours. However, new prospective randomized clinical trials have shown that in children under the age of 7 with mild to moderate amblyopia 2 hours of daily patching is as effective as 6 hours of treatment.

Poor compliance with therapeutic patching regimens has often been cited as a major problem with occlusion treatment due to the extreme emotional reactions of children prescribed patching therapy and the visual impact of wearing the patch.

Pharmacological penalization, typically with atropine sulphate eye drops, offers an alternative treatment for amblyopia which is reported to be easier for parents to administer and may be more cosmetically acceptable for the child. In a trial of 193 children 7-12 years old with moderate amounts of amblyopia, both atropine and patching led to similar degrees of improvement in visual acuity, with approximately 20% of  patients reaching 6/7.5 acuity or better in the amblyopic eye by their final follow-up visit. However, concern exists over the potential side effects of atropine (hypersensitivity, central nervous system disturbance, loss of co-ordination, hallucinations, respiratory depression and systemic hypotension). The most common side effects reported were ocular redness (28%) and light sensitivity (16%); systemic side effects were rare and only reported in 3% of participants (1 patient reported tachycardia, 1 dry mouth and 1 had headache and irritability).

A number of factors have been identified that may influence the outcome of amblyopia therapy. The presence of eccentric fixation, severely reduced initial visual acuity in the amblyopic eye, and no binocular function have all been identified as factors associated with a poor treatment outcome, while anisometropic amblyopia has a better prognosis and can show response to treatment in older age groups.

In conclusion, atropine and patching appear to be equally effective in the treatment of moderate amblyopia in patients as old as 12 years. The response to therapy may be more rapid in patients undergoing patching therapy; however atropine penalization remains an option for children in which compliance may be an issue.

Ophthalmology View – Rasha Al-Taie

Amblyopia is common, with prevalence estimates of between 1 and 3%. It is the most frequently treated disorder in paediatric ophthalmic and orthoptic practice. The diagnosis of amblyopia is not straightforward because of the difficulties in testing vision in small children and uncertainties about the contribution made to any visual abnormality by refractive error and ocular pathology.

It is important to recognise that a finding of reduced visual acuity in a child is not a diagnosis of amblyopia. Amblyopia is only found in the setting of a causative factor such as strabismus or refractive error. If no obvious amblyogenic factor is found on examination then either the reliability of the visual acuity measurement should be questioned, or subtle ocular pathology needs to be excluded. 

This case highlights a few important issues in the management of an isometropic Amblyopia. First, it illustrates that ansiometropic hyperopia of >1 diopter can be amblyogenic. Second, refractive error correction alone can improve amblyopia. This has been established by the PEDIG (Paediatric Eye Diseases Investigator Group) who showed refractive error correction resulted in resolution of amblyopia occurred in one third of 3-7 year-old children and VA improved in many other cases. In this case, the child was treated with glasses alone for 2 years and the VA improved from 6/36 to 6/15. The case also shows the importance of attending follow up appointments following the initial treatment. The recommended practice once the glasses have been prescribed is to review the child within 2-3 months to re-assess the vision. If there is improvement in VA then the child should continue with glasses, but if there is no improvement in VA, re-examination including cycloplegic refraction is recommended. Improvement in acuity following refractive correction should be allowed to plateau for weeks before considering further management with patching or penalization.

However in this case the child failed to attend the regular follow up appointment which resulted in delays in further management for over 4 years at a crucial time period in the management of amblyopia.

It is well established that both atropine and patching are as effective in treatment of moderate amblyopia (20/40-20/100). Patching has the potential advantages of a more rapid improvement in visual acuity initially, whereas the advantages of atropine are that the treatment is not cosmetically obtrusive, and that compliance is not an issue once the drops or ointment are instilled. The disadvantages are that it is less easy to monitor for occlusion amblyopia and that systemic side effects, such as flushing, hyperactivity and tachycardia may occur, particularly in young children and those with Down’s syndrome. Because the burden of amblyopia treatment lies with the parents, in this case, due to shared parental custody and previous compliance issues, the use of atropine was very appropriate, on condition that the sound eye is monitored very closely. Regarding the atropine regime, weekend atropine provides an improvement in VA of a magnitude similar to that of the improvement provided by daily atropine in treating moderate amblyopia in children 3 to 7 years, although the regime has to be adjusted according to the density of ambylopia and the response of each child to treatment.

Of note, around 25% of successfully treated amblyopic children experience a recurrence within the first year off treatment. There is a suggestion that the risk of recurrence is greater when patching is stopped abruptly. Many children will have a residual visual deficit despite compliance with treatment. This is worth explaining to the carer when treating a child with amblyopia.

In conclusion, this case shows a few of the difficulties in the management of amblyopia which are a common in clinical practice and the importance of considering all these factors when we choose treatment modalities.

References

Rahi, J., et al., Risk, causes, and outcomes of visual impairment after loss of vision in the noamblyopic eye: a population-based study. Lancet, 2002. 360(9333): p. 597-602.
Repka, M.X., et al., A randomized trial of patching regimens for treatment of moderate amblyopia in children. Arch Ophthalmol, 2003. 121(5): p. 603-11.
Scheiman, M.M., et al., Patching vs atropine to treat amblyopia in children aged 7 to 12 years: a randomized trial. Arch Ophthalmol, 2008. 126(12): p. 1634-42.
Stewart, C.E., et al., Treatment of unilateral amblyopia: factors influencing visual outcome. Invest Ophthalmol Vis Sci, 2005. 46(9): p. 3152-60.
Wick, B., et al., Anisometropic amblyopia: is the patient ever too old to treat? Optom Vis Sci, 1992. 69(11): p. 866-78.
Cotter SA, Pediatric Eye Disease Investigator G, Edwards AR, et al. Treatment of anisometropic amblyopia in children with refractive correction. Ophthalmology. Jun 2006;113(6):895-903.
Pediatric Eye Disease Investigator G. A randomized trial of atropine vs. patching for treatment of moderate amblyopia in children. Archives of Ophthalmology. Mar 2002;120(3):268-278.
Repka MX, Cotter SA, Beck RW, et al. A randomized trial of atropine regimens for treatment of moderate amblyopia in children. Ophthalmology. Nov 2004;111(11):2076-2085.
Holmes JM, Beck RW, Kraker RT, et al. Risk of amblyopia recurrence after cessation of treatment. Journal of Aapos: American Association for Pediatric Ophthalmology & Strabismus. Oct 2004;8(5):420-428.

* Nicola Anstice is an optometrist at the Manukau SuperClinic, South Auckland and a Lecturer at the Department of Optometry and Vision Science, The University of Auckland. She has a special interest in paediatric vision.
Rasha Al-Taie is currently the Paediatric Fellow at Greenlane Clinical Centre Ophthalmology department, and will be taking up a post as Consultant at Manakau Superclinic Ophthalmology Department in December 2010, specialising in general and paediatric ophthalmology.

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