Ophthalmology Times Europe March 2016 by Erica Crompton

C U T T I N G - E D G E A DVA N C E M E N T S MARCH 2016 VOL. 12, NO. 2

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CU T TING - EDGE ADVANCEMENT S MARCH 2016 VOL. 12, NO. 2

ISSUE FEATURE

PROGRESSIVE APPROACHES IN RETINA BEFORE

New concepts in DME therapy Treating diabetic macular oedema with second-line steroids CATARACT & REFRACTIVE AFTER

Hitting the visual sweet spot A new class of IOLs for highly satisfied patients BEFORE. Pre-injection AFTER. The same eye after the injection (Images courtesy CareUK)

GENERAL

Overseas sights How an art sale at Sothebyâ&#x20AC;&#x2122;s helped cataract patients in Nepal

WET AMD

REAL-WORLD STRATEGIES Achievement of clinical trial outcomes PAGE 6

The Essence of Perfection For Retina, Cataract and Glaucoma Surgery s HDC Control for maximum precision, safety and surgery control s Newly developed vacuum and ﬂow tri-pump system s SPEEP® mode for very precise maneuvers s Active and gravity infusion s Up to 10’000 cuts with the Continuous Flow-Cutter s Double light source with color adjustable LED technology s Fully integrated 532 nm green endo laser s Brand new phaco engine for even more efﬁciency and safety s Wireless, dual linear all-in-one foot switch s Intuitive user interface with Direct Access® s Embedded Controller Technology for utmost system performance

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March 2016 l Volume 12 Number 2

contents 31 Adjustable intraocular lenses after cataract surgery IOL exchange following cataract surgery can be difficult.

Glaucoma 34 Redefining cyclophotocoagulation MicroPulse transscleral cyclophotocoagulation is an effective, affordable and safe technique to lower IOP in patients with glaucoma.

Focal Points

13 Issue Features 06 Clinical trial outcomes with ranibizumab This paper reconfirms this finding in the treatment of wet age-related macular degeneration (wet AMD).

10 Advancing diagnostics Early detection and treatment is essential to preserve vision in patients with age-related macular degeneration.

13 Latest concepts in steroid therapy Steroids are an important second-line treatment for the treatment of diabetic macular oedema.

17 Diabetic macular oedema pharmacotherapy in practice Many pharmaceutical treatments are available and in development for the treatment of diffuse diabetic macular oedema.

20 Gene therapy for neovascular age-related macular degeneration The results are disappointing, but do not necessarily spell the end of the investigational product’s development.

Cataract & Refractive 22 Novel trifocal IOL extends range of vision Early results for visual acuity, contrast sensitivity, and photopic symptoms are encouraging.

24 Are extended-depth-of-focus IOLs hitting the spot?

37 A case report of a torcular dural AV fistula DAVF (Intracranial dural arteriovenous fistula) is thought to be an acquired arteriovenous (AV) shunting disease, perhaps developing after venous sinus occlusion.

39 Sale at Sotheby’s helps restore sight A Gerhard Richter painting donated to CBM by an anonymous donor has raised 44,500 Euros at a Sotheby’s auction.

Regulars 40 Product news

Current IOL designs offer a variety of optical options for the correction of presbyopia.

28 Clinical experience with a mechanical pupil dilator Cataract patients with small pupils present a particular challenge for surgeons.

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MARCH 2016 :: Ophthalmology Times Europe

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IS SU E F E AT U R E

Progressive approaches in retina Real-world strategies for wet AMD In many clinical areas, early consultant-led intervention has been shown to improve clinical and patient-reported outcomes and to reduce overall treatment costs. This paper reconfirms this finding in the treatment of wet age-related macular degeneration (wet AMD) and presents data from a publicly funded NHS fast-track (FT) centre in north-west England that aims to see and treat patients within 48 hours of referral. Karen Goodall Adam Levy Reviewed by Winfried Amoaku, associate professor/ reader and honorary consultant ophthalmologist at the University of Nottingham, and Nottingham University Hospitals Trust

n many clinical areas, early consultant-led intervention has been shown to improve clinical and patient-reported outcomes and to reduce overall treatment costs. This paper reconfirms this finding in the treatment of wet age-related macular degeneration (wet AMD) and presents data from a publicly funded NHS fast-track (FT) centre in north-west England that aims to see and treat patients within 48 hours of referral. Outcomes, in this real-world setting and at commissioning scale, exceed those from clinical studies. National treatment guidelines are not onerous but are nevertheless often not met, and this paper reinforces the clinical benefits of early and on-protocol treatment and the consequent importance of patient, provider and commissioner education. Given the cost to patients and society of poor compliance and outcomes, we call for systematic monitoring of performance metrics on a national scale.

Background Wet AMD is a common eye condition that leads to rapid and progressive loss of central vision and severe visual impairment. Two agents, the anti-vascular endothelial growth factor (VEGF) antibody ranibizumab (Lucentis, Novartis) and the VEGF trap aflibercept (Eyelea, Bayer), have been shown to be highly effective in inhibiting the neovascularisation that is characteristic of wet AMD and stabilising or improving vision in most patients. Two pivotal randomised controlled trials, ANCHOR1 and MARINA,2 underpin the use of intravitreal ranibizumab in the treatment of

We set out to build a wet AMD service able to confirm a diagnosis of wet AMD and initiate VEGF inhibition within 48 hours. wet AMD. In the ANCHOR study, in which ranibizumab was administered on a fourweekly basis over two years, visual acuity (VA) improved by 15 or more letters in 40.3% of patients, with a mean improvement of 11.3 letters at one year and 10.7 letters at two years.

Background (cont.) The MARINA study showed that, at 12 months, 94.6% of patients had lost fewer than 15 letters of vision, VA had improved by 15 or more letters in 33.8% of patients and the overall mean improvement was 7.2 letters. The PrONTO study3 subsequently demonstrated the equivalent effectiveness of pro re nata (PRN) administration after initial stabilisation of the lesion, using optical coherence tomography (OCT) parameters to dictate treatment. Mean VA increased by 9.5 letters at 12 months and 10.7 letters at 24 months. Baseline vision was maintained by 78% of patients

IN SHORT Achievement of clinical trial outcomes with ranibizumab in a real-world setting: oneyear results from implementation of 48-hour referral-to-injection treatment of wet macular degeneration

MARCH 2016 :: Ophthalmology Times Europe

ISSUE FE ATURE

Progressive approaches in retina

Box 1. PRN protocol for the management of wet AMD

Day 0

LogMAR VA on arrival, OCT of both maculae Images reviewed by retinal consultant or consultant competent in OCT review FFA booked to confirm diagnosis Patient directly listed for series of 3 ranibizumab (Lucentis, Novartis) injections at 4-week intervals as per NICE inclusion criteria. Injection as per RCOphth guidelines5

After

Follow-up (FU) visit with AMD nurse every 4 weeks =/- 3 days

third injection

LogMAR VA, OCT of both maculae If OCT shows lesion activity denoted by persistent fluid, new haemorrhage or a loss of LogMAR letters, further injection indicated within 1 week If no activity, AMD specialist FU at 4 weeks +/= 3 days

Nonresponders

No response to treatment after 8 injections: consider switch to aflibercept

(BOX 1) PRN protocol for the management of wet AMD

and VA improved by 15 letters or more in 43% of patients. Subsequent ranibizumab studies have further improved these treatment models, including the validation of treat and extend, which achieves similar outcomes.4 The overall effectiveness of all of these pathways depends on both the time from symptom onset to treatment initiation and compliance with subsequent treatment protocols. Although the Royal College of Ophthalmologists recommends treatment within two weeks of initial referral, 5 many, if not most, providers routinely fail to achieve these targets and realworld results fall considerably short of those expected from clinical trials. 6â&#x20AC;&#x201C;8. This is generally attributed to capacity constraints reducing treatment frequency, case-mix, www.oteurope.com

loss of patients to follow-up and difficulty with transportation.9 On the other hand, it is widely acknowledged that early and protocol-compliant consultant-led intervention improves outcomes and reduces overall healthcare journey costs in a range of disease areas. 10 This paper re-examines this principle in the treatment of wet AMD, and reports one-year data from a newly established fasttrack service that aims to see and treat patients within 48 hours of referral, in strict accordance with existing PRN protocols.

Fast-track treatment of wet AMD We set out to build a wet AMD service able to confirm a diagnosis of wet AMD and initiate VEGF inhibition within 48 hours of referral. This timeline was selected as being ambitious yet

deliverable within the constraints of the normal Monday-to-Friday working of a secondary care ophthalmology unit. By building a responsive and flexible capacity, able to urgently accommodate the patient on the day of referral or the following day and to initiate treatment at the same visit, only patients mis-directed through non-FT gateways, those unwilling or unable to present urgently or those referred at close of day on a Friday would necessarily fall outside of the 48-hour window. Following a consultantdelivered optometrist education programme, a direct fax-based FT pathway was established across a clinical commissioning group (CCG) area for the urgent referral of all cases of suspected AMD. Upon referral, patients are immediately telephoned by an AMD specialist nurse, advised of

ISSUE FE ATURE

Progressive approaches in retina

120.0%

100.0%

>14 days

80.0%

<14 days <7 days

60.0%

<48 hours <24 hours

40.0%

Same day 20.0%

0.0% Non FT

Fast-track

(FIGURE 1) Cumulative referral to injection time performance for fast-track and nonfast-track patients. Colours indicate compliance with existing RCOphth guidelines.(5)

Mean VA change

10 5 0 0

-5 -10 -15

Time / months from first injection All patients

FT patients

Anchor

Marina

Sham

(FIGURE 2) Mean VA change in fast-track and all-patient treatment groups.

the importance of early disease intervention and offered an appointment that day or the next. Beginning the process of informed consent and expectation management, patients are advised that treatment may be required at the first visit and given a 24/7 contact number for the service. Upon attendance, the patient is treated exclusively by the same specialist AMD nurse, who conducts diagnostic tests including LogMAR vision and

OCT (Spectralis, Heidelberg) and arranges fluorescein angiography for a second visit. Results are discussed with a sub-specialist retinal consultant and a definitive diagnosis made at the first presentation using well-established and widely used clinical protocols. Following a diagnosis of wet AMD and establishment of eligibility under NICE guidelines, patients are listed directly for intravitreal injection, accommodated within

existing cataract procedure scheduling or included in a dedicated injection list. Injections are conducted in a sterile operating environment, using established methods and protocols, by ophthalmic consultant surgeons and a specialist AMD nurse. Following the first appointment, the referring optometrist is telephoned by the AMD nurse and informed of the patientâ&#x20AC;&#x2122;s clinic attendance and diagnosis. Injections and follow-up investigations are conducted according to existing PRN pathways as shown in Box 1.

One-year results Overall, 165 patients from a single CCG were referred to the newly established macular service during the 15-month period from September 2014, with 73 (44.2%) referred through the accelerated (FT) channel, and the remainder through routine non-FT pathways. The wet AMD diagnosis was confirmed in 62 (84.9%) FT and 22 (23.9%) non-FT patients who were treatment naive and met the criteria for treatment with Lucentis. Fourteen patients had bilateral disease; therefore, 98 eyes in total were treated. One patient was excluded from the study on leaving the country and two patients suffered unrelated excluding events. Figure 1 shows referral to treatment time performance for FT and non-FT groups. In the FT group, 56.8% of patients were seen and treated within 48 hours of referral, with 94.8% seen and treated within one week. The equivalent figures for non-FT patients are 21.4% and 52.4%, respectively. The subsequent treatment of 84% of patients (both FT and non-FT) was fully compliant with the Box MARCH 2016 :: Ophthalmology Times Europe

ISSUE FE ATURE

Progressive approaches in retina 1 protocol for all appointments and injections, with remaining patients deviating by less than two weeks, largely as a result of patient availability. Figure 2 shows the resulting mean improvement in VA over the 12-month period: 7.2 letters for all wet AMD patients and 8.8 letters for FT patients. In 95.3% of patients, VA deteriorated by less than 15 letters; 30.2% of patients had an improvement of more than 15 letters. Baseline vision was maintained or improved in 81.4% of patients.

Comment Despite a failure to meet the target to see and treat every single patient within 48 hours of referral, results from the service are highly consistent with those of the ANCHOR and MARINA studies and suggest that the level of performance achieved in clinical trials is achievable in real-world practice through earlier intervention and improved protocol adherence. The relative contribution of these elements merits further investigation. Implementation of treatment within 48 hours is not, however, without challenge. Notably, despite consultant-delivered education and one-to-one feedback, patients continued to be referred through non-urgent channels. Achievement of see-andtreat targets were also limited by patient lack of readiness to undergo intravitreal injection as an urgent procedure, despite attempts to manage patient expectations from the first contact. Inevitably, some patients were also unable to be accommodated urgently within existing activities and there was a continual need to reinforce clinical urgency www.oteurope.com

in scheduling practices more normally used to elective activity. Nevertheless, existing routine activity need not be dramatically disturbed by the integration of urgent pathways; although secondary care ophthalmology is usually treated as a scheduled care specialty with limited requirement for acute unplanned activity, the service described here was developed with limited impact on the existing pathways with which it shares equipment, operating facilities and staff. This was achieved through the real-time adjustment of capacity and resource allocation based on demand, supported by a detailed administrative and booking framework. An integrated team commitment to the delivery of gold-standard care across all pathways was further motivated by significant patient success stories. This ability of the service to provide treatment at short notice improved throughout the period of study as a result of increased experience and the existence of dedicated injection lists primarily occupied by follow-up patients. This would indicate that existing providers could perhaps adapt readily to firmer treatment scheduling.

Concluding comments This paper describes our experience of establishing a 48-hour wet-AMD treatment service and demonstrates that reference-standard outcomes are achievable in the real-world setting, at typical (250,000 population) commissioning scale and at no additional cost over existing pathways. Nationally, wet AMD services are highly variable and it is likely that the vision of several thousand UK patients per year, along with the estimated costs

associated with blindness, could be saved through faster, protocolcompliant wet AMD pathways. This paper highlights the importance of educating providers, commissioners and healthcare regulators to expect, monitor and enforce higher standards in the treatment of wet AMD and, given the considerable personal and societal costs of sight loss, we propose urgent implementation of centralised systematic performance monitoring on a national scale.

REFERENCES 1. D.M. Brown et al., Ophthalmology 2009; 116(1): 57-65.e5. 2. P.J. Rosenfield et al.,N. Engl. J. Med. 2006; 355(14): 1419-1431. 3. G.A. Lalwani et al., Am. J. Ophthalmol. 2009; 148(1): 43-58.e1. 4. J.J. Arnold et al., Ophthalmology 2015; 122(6): 1212-1219. 5. Royal College of Ophthalmology. Guidelines on the management of macular disease. September 2013, p106. 6. Writing Committee for the UK Age-Related Macular Degeneration EMR Users Group. Ophthalmology 2014; 121(5): 10921101. 7. R. Chevan et al.,Clin. Ophthalmol. 2014; 8: 717-723. 8. F.G. Holz et al., Br. J. Ophthalmol. 2014. Published online first on Sept. 5 th 2014. doi:10.1136/bjophthalmol- 2014305327 9. London Medicines Evaluation Network Review. Evidence behind change in treatment regimen recommendations and monitoring for ranibizumab and data on use in clinical practice for age related macular degeneration. September 2014. 10. Academy of Medical Royal Colleges. The benefits of consultant-delivered care. London: AMRC, 2012.

KAREN GOODALL E: Karen.Goodall@careuk.com Care UK, the UKâ&#x20AC;&#x2122;s largest independent healthcare provider, and Manchester Consultants Eye Partnership (MCEP), a local consultant consortium, together provide an NHS ophthalmology service for around 250,000 patients in Rochdale, England. The service delivers a full range of gold-standard secondary level activities in a community setting.

IS SU E F E AT U R E

Progressive approaches in retina Preserving vision with advanced diagnostics Early detection and treatment is essential to preserve vision in patients with age-related macular degeneration. A new device, the ForeseeHome, uses preferential hyperacuity perimetry for early detection of choroidal neovascularisation before symptoms develop. Richard Garfinkel, MD

he damage caused by age-related macular degeneration (AMD) can develop slowly or quickly, and the early and intermediate stages often pass without symptoms. While a complete dilated eye examination will allow an ophthalmologist to detect the disease, a patient often does not notice it until their central vision is significantly deteriorated. Unfortunately, the outcomes of AMD treatment depend on baseline visual acuity, area and characteristics of choroidal neovascularisation

Understanding the necessity of self-monitoring of disease, it became common in the 1960s to provide Amsler grids to patients. (CNV)1 and, while new pharmaceutical treatment options have made great strides in terms of maintaining patientsâ&#x20AC;&#x2122; vision, restoration of significant vision loss is rare. This shifts the burden of disease management to the earliest detection of CNV, so that the best vision possible can be preserved. While there are known risk factors, there is no true predictive model for determining who will progress from dry to wet AMD and when; and the typical six-month interval between eye-care appointments could allow an alarming amount of disease progression and visual loss. Understanding the necessity of self-monitoring of disease, it became common in the 1960s to provide Amsler grids to patients. Although this has been the standard of care for more than half a century, limitations such as perceptual completion and lack of compliance make the overall sensitivity for detecting macular disease much less than 50%.2,3

IN SHORT (FIGURE 1) Use of a home vision-monitoring device by patients may help detect early signs of a serious problem related to CNV before there are obvious symptoms, and clinicians may be able to start treatment immediately. (Photo courtesy of Notal Vision)

The ForseeHome device gives dramatic improvements in monitoring the progression of age-related macular degeneration, allowing patients to maintain their vision.

MARCH 2016 :: Ophthalmology Times Europe

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Images courtesy of Bruno Lumbroso, MD, Rome, Italy. Colorization per Oregon Health Science University PN 302-51068 Rev A

ISSUE FE ATURE

Progressive approaches in retina Hyperacuity is the ability to perceive minute differences in the relative spatial localisation of two objects, a human skill that remains despite ageing and cataract development.4–6 However, changes in retinal morphology lead to an incorrect perception of the location of the objects. Preferential hyperacuity perimetry (PHP) assesses and records perceived shifts in object location that correlate to metamorphopsia.7 When this is compared with a patient’s baseline and normative data for an AMD population, it becomes an effective test for detecting the development of CNV.8 Further developments with PHP include the ForseeHome device (Notal Vision), which patients can use in their own homes. In addition to the improved efficacy of PHP over the Amsler grid, Notal Vision monitors patients’ use of the ForeseeHome device, receiving real-time test results. By following up with patients who are not consistent with their home vision monitoring, many of the common compliance obstacles are overcome. The HOME study, a subset of the AREDS2 study, compared the use of the ForseeHome device plus standard care with standard care alone in more than 1500 patients with a high risk of progression to CNV.9 The interim analysis, 1.4 years into the study, found sufficient advantage to the use of the device that the Data and Safety Monitoring Committee recommended an early study termination. Participants in the device cohort lost a median of four EDTRS letters while those in the standard care group lost a median of nine letters (P=0.021).

Clinical use I have been using the ForseeHome device with my patients since 2011, even before the HOME study began, and our experience has mirrored

the study data. The monitoring centre sends our practice an email alert when a patient has a sufficiently abnormal test result and we call the patient into the office, within 24 hours in most cases. Nearly every time, the patient responds that they are fine and the machine had malfunctioned; however, we have often found that the device had detected early signs of a serious problem related to CNV, before there were obvious symptoms, and were able to start treatment immediately. The alternative arrangement for such early detection would be extremely frequent patient examinations, which is highly impractical. This is dramatically different from what happens when a patient is relied upon to use the Amsler grid and contact their doctor when symptoms are experienced. Even in the best cases, with patients that do test frequently, are able to fixate centrally and do not experience any neurological interference, human nature is to deny that there is a problem until it is so severe that it is interfering with function. At this point, a significant amount of vision has been lost and is unlikely to be restored completely. If we can detect progression before vision declines beyond 20/40, we can preserve our patient’s lifestyle. They do not lose the ability to drive, navigate alone or recognise and remain connected to individuals. Patients who have lost their independence often comment that they would pay anything to restore their vision. With this in mind, I do not make any attempt to determine whether a patient can afford the home monitoring device. As a physician, my job is to educate patients, present their options and then tell them my professional opinion of what is best. I tell them that the device is not presently covered by insurance, although

the company is working towards that end, and let them know the monthly cost associated with the ForseeHome device. I find that the vast majority of my eligible patients do elect to pay, and find great benefit in the device. The HOME study data show that over 90% of patients using the ForseeHome device as recommended are able to detect disease progression and maintain vision better than 20/40, whereas only 62% in the control group had the same chance of keeping their vision. That is a dramatic difference. PHP monitors actual diagnostic signs of AMD progression, independent of visual acuity, and aids in medically managing patients in a way that has not been possible previously.

REFERENCES 1. G.S. Ying et al., Ophthalmology 2012; 120(1): 122-129. 2. M. Crossland and G. Rubin. Br. J. Ophthalmol. 2007; 91(3): 391-393. 3. R.A. Schuchard. Arch. Ophthalmol. 1993; 111(6): 776-780. 4. G. Westheimer. Invest. Ophthalmol. Vis. Sci. 1979; 18(9): 893-912. 5. J.M. Enoch et al.,Arch. Ophthalmol. 1984; 102(8): 1164-1168. 6. V. Lakshminarayanan, S. Aziz and J.M. Enoch. Optom. Vis. Sci. 1992; 69(6): 423-426. 7. A. Loewenstein et al.,Ophthalmology 2003; 110(5): 966-970. 8. J.S. Heier et al., Ophthalmology 2005; 112(10): 1758-1765. 9. AREDS2-HOME Study Research Group. Ophthalmology 2014; 121(2): 535-544.

DR. RICHARD GARFINKEL E: rgarfinkel@rgw.com Richard A. Garfinkel, MD, practices with The Retina Group of Washington in Virginia, Maryland and Washington, DC. Dr Garfinkel has hospital appointments at Washington Hospital Center, Inova Fair Oaks Hospital and Friendship Surgery Center. He is also a clinical assistant professor at Georgetown University and has a courtesy appointment at Inova Fairfax Hospital. MARCH 2016 :: Ophthalmology Times Europe

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Progressive approaches in retina Latest concepts in steroid therapy for diabetic macular oedema Steroids are an important second-line treatment for the treatment of diabetic macular oedema. While side effects remain a concern, modern formulations of intravitreal steroid allow the treatment to be tailored to the individual patient. Dr Margaret A. Greven, Dr Peter Karth Reviewed by Professor Pavel Kuchynka, MUDr, CSc, FCMA

iabetic macular oedema (DME) is the leading cause of visual impairment in patients with diabetes. It has been estimated that approximately 93 million people in developed nations are affected with diabetic retinopathy, 21 million of whom have DME. A study showed that the prevalence of DME in the US is 3.8%, with risk factors being elevated haemoglobin A1c levels and longer duration of diabetes.1 The increasing number of patients with diabetes worldwide suggests that the impact of DME on vision loss as well as functional impairment will continue to grow over the coming years. DME results from breakdown of the blood–retinal barrier and increased vascular permeability mediated by inflammatory cells, cytokines and other inflammatory mediators including vascular endothelial growth factor (VEGF). This increased permeability results in

“After three years, incisional glaucoma surgery was needed in 4.8% of patients in the low-dose group.” accumulation of intraretinal fluid and macular thickening. The most commonly used treatments for DME target the VEGF molecule; however, we have recently become more aware of other mediators of this condition to target, especially in cases refractory to anti-VEGF therapy. The efficacy of corticosteroids in DME has been shown in multiple clinical trials. The effectiveness of steroids in the treatment of DME results from multiple mechanisms. Recruitment of leukocytes, production of adhesion molecules, up-regulation of prostaglandins and accumulation of macrophages within the retina occur in diabetes, and steroids are nonspecific anti-inflammatory agents that inhibit these processes. Steroids also stabilise the blood–retinal barrier and reduce capillary permeability by inhibiting leukocyte recruitment and enhancing the activity of endothelial cell tight junctions.2,3 Furthermore, steroids inhibit the action of VEGF and regulate its

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(FIGURE 1) (Photo courtesy of Dr Peter Karth) www.oteurope.com

Steroids are an important second-line treatment for the treatment of diabetic macular oedema. While side effects remain a concern, modern formulations of intravitreal steroid allow the treatment to be tailored to the individual patient.

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TABLE 1: Comparison of ranibizumab and corticosteroid options for the treatment of DME.

Drug Ranibizumab

Duration 1 month

Trial

VA improvement

RISE/RIDE [19]: Ranibizumab 0.3 mg or 0.5 mg compared to sham

* 15 letter improvement (RISE/RIDE) 0.3 mg: 44.8%/33.6% 0.5 mg: 39.2%/45.7% Sham: 18.1%/12.3%

Complications Cataract: RISE no cataract reported RIDE 0.8% cataract (low dose), 1.6% (high dose) Glaucoma: RISE: none RIDE: Intraocular pressure rise in 0.8% (high dose)

Triamcinolone acetonide

2-4 months

Gilles et al [6]: IVTA compared to placebo

* 5 letter improvement TA: 56% Placebo: 26%

Cataract: 54% of treated required cataract surgery Glaucoma: medication in 44% treated and no untreated, surgery in 5.9% of treated

DEX Implant (Ozurdex)

4-6 months

Boyer et al [14]: DEX 0.7 mg or 0.35 mg compared to sham

* 15 letter improvement DEX 0.7 mg: 22.2% DEX 0.35 mg: 18.4% Sham: 12%

Cataract: in phakic patients, 67.9% (high dose), 64.1% (low dose), and 20.4 % (sham) developed cataract Glaucoma: surgery in 0.3% (low dose) and 0.6% (high dose)

Fluocinolone acetonide (Iluvien)

3 years

Campochiaro et al [16]: Iluvien 0.2 ug or 0.5 ug compared to sham

* 15 letter improvement 0.2 ug: 28.7% 0.5 ug: 27.8% Sham: 18.9%

Cataract: in phakic patients, 80%(low dose), 87.2% (high dose) and 27.3% (sham) required cataract surgery Glaucoma: At 3 years, surgery in 4.8% (low dose) and 8.1% (high dose)

Fluocinolone acetonide (Retisert)

3 years

Pearson et al [18]: Retisert 0.59 mg compared to grid laser

* 15 letter improvement 0.59 mg: 31.8% Sham: 9.3%

Cataract: 91% of phakic patients in treatment group required cataract surgery Glaucoma: At 4 years, surgery in 33.8% in 0.59 mg group

expression, thereby directly affecting permeability and angiogenesis,4,5 in addition to regulating a number of other peptides involved in the inflammatory processes leading to DME. The side effects of steroids are a concern, especially in the era of anti-VEGF medications that have few ocular side

effects. The main side effects of intravitreal corticosteroids for DME are cataract progression and glaucoma. For this reason, steroids are typically considered relatively contraindicated in patients with glaucoma or ocular hypertension. The question remains: How do todayâ&#x20AC;&#x2122;s steroid options fit into the treatment of patients with DME?

Triamcinolone acetonide Intravitreal triamcinolone acetonide (IVTA) is more effective than placebo at improving vision in patients with refractory DME;6 its efficacy has been studied in multiple clinical trials.1-11 The Diabetic Retinopathy Clinical Research Network protocol I reported IVTA plus laser to have MARCH 2016 :: Ophthalmology Times Europe

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Progressive approaches in retina equivalent efficacy to ranibizumab plus laser in pseudophakic patients at two years.10,11 More recently, combination therapy with IVTA plus anti-VEGF injections has been shown to have more benefit than anti-VEGF injections alone for some patients with DME.12 IVTA is available in four preparations: Triesence, Trivaris, Kenalog and preservative-free triamcinolone acetonide prepared by compounding pharmacies. All of these formulations are offlabel for DME. Kenalog, which contains preservatives, is not FDAapproved for intraocular use, but is commonly used off-label.13 Triesence and Trivaris have been approved by the US FDA for intravitreal injection and are prepackaged and preservative free, thus avoiding the potential for sterile inflammatory reaction to preservative found with Kenalog, or potential contaminants in the compounded triamcinolone acetonide. Triesence and Trivaris are much more costly than Kenalog and compounded TA. IVTA must be repeated every two to four months to sustain effect. To address this need for frequent retreatment, sustainedrelease preparations of intravitreal corticosteroid have been developed.

Ozurdex Ozurdex (Allergan, Irvine, CA) is a sustained-release biodegradable 0.7 mg dexamethasone (DEX) implant with duration of action of four to six months, which is approved by the FDA for the treatment of DME in pseudophakes and patients scheduled for cataract surgery. In two three-year parallel phase III randomised clinical trials in which patients were given either DEX 0.7 mg implant, DEX 0.35 mg implant or sham procedure, www.oteurope.com

IVTA must be repeated every two to four months to sustain effect. 22.2%, 18.4% and 12% of patients, respectively, met the primary end point of at least a 15-letter visual acuity gain from baseline.14 Although there were high rates of cataract development in both DEX groups compared with sham, only two patients in the 0.7 mg group and one in the 0.35 mg group required incisional glaucoma surgery.14 A subgroup analysis of patients who had previously been treated for DME found that 21.5% of patients who received DEX 0.7 mg, compared with 11.1% of sham, met the primary endpoint.15 These trials demonstrated the efficacy of Ozurdex for DME treated primarily, as well as refractory to previous treatment or in vitrectomised patients. The advantages to using this strategy for DME are a longer duration of action, up to six months, and clinical efficacy in patients unresponsive to other treatments. The disadvantage of Ozurdex use is that, like other intraocular corticosteroid treatments, it leads to cataract in most patients and, in some, to elevated IOP.

Iluvien Iluvien (Alimera, Alpharetta, GA) is a new extended-release fluocinolone acetonide nonbiodegradable injectable device with duration of action of three years, which is approved by the FDA for treatment of DME in patients who have been previously treated with a course of corticosteroids and did not have a significant pressure response.

The efficacy of Iluvien in DME was established by the FAME studies, two parallel phase III randomised clinical trials in which patients were randomised 1:2:2 to sham injection, 0.2 mg/day insert and 0.5 mg/day insert. The primary endpoint of the study was the percentage of patients with an improvement of 15 or more letters from baseline. At two years, both the lowand the high-dose treatment groups had approximately 28% of patients achieving this endpoint, compared with 16% of patients who had received sham injection.16,17 At three years, there was a sustained visual acuity improvement, which was more significant for patients who had a duration of DME of at least three years compared with those with shorter duration.17 Almost all phakic patients who received the implant developed cataract; however, visual improvement in these patients after cataract surgery was the same as in those who were pseudophakic at baseline. After three years, incisional glaucoma surgery was needed in 4.8% of patients in the low-dose group and 8.1% of patients in the high-dose group. Importantly, in the low-dose group, visual outcomes were equivalent in patients who had and did not have glaucoma surgery.17 Iluvien offers particular promise for patients with longstanding DME refractory to other treatments, as well as difficultto-treat vitrectomised eyes, given its long duration of action. An additional benefit is far fewer injection procedures, although frequent monitoring for pressure elevation is still required. Its disadvantages include cataract and IOP rise, as for other intraocular steroid formulations.

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Progressive approaches in retina Retisert Retisert (Bausch + Lomb, Rochester, NY) is a surgically implanted sustained-release fluocinolone acetonide 0.59 mg pellet with duration of action of approximately three years. The implant is placed by suturing through a scleral incision at the pars plana. Retisert is not FDA approved for DME but its use has been studied in this condition. In a randomised clinical trial comparing Retisert with grid laser in patients with refractory DME, 31.8% of patients who received Retisert compared with 9.3% who received grid laser met the endpoint of 15 letters’ improvement in vision at two-year follow-up.18 Although the potential efficacy of the device was demonstrated in this study, of the patients who received Retisert, 91% of phakic eyes required cataract surgery and 33.8% of patients required glaucoma surgery at four years. With these high rates of complications, the need for incisional surgery to implant the device, and its significant cost, this option is not widely used for DME.

Conclusion Although intravitreal anti-VEGF injections (with or without laser) have become the first-line treatment for DME because of excellent efficacy and low rate of complications, steroids can be used, often with excellent response, in patients with suboptimal response to anti-VEGF therapy. The longer duration of action of steroid therapies compared with anti-VEGF treatment is certainly a factor to consider, although this is somewhat offset by the need for frequent visits for IOP monitoring. At our institution, we typically employ a stepwise approach

for the treatment of DME, beginning with a course of three to six monthly injections of bevacizumab in patients with DME. Suboptimal responders are changed to aflibercept for at least three monthly injections. In those patients who still have suboptimal response, we next use a preservative-free formulation of IVTA to gauge response in terms of efficacy as well as IOP. If IOP remains within the normal range, IVTA can be repeated every three to four months, or longer-acting steroid preparations may be used. Interestingly, we have seen several patients have a poor response to IVTA but an excellent response to Ozurdex. We often move more quickly to steroid therapy in vitrectomised patients. A newer therapy that offers significant promise is the fluocinolone acetonide implant. At our institution, we are beginning to use this formulation in select patients and to determine where it fits into our treatment algorithm. Most likely, those patients with excellent response to bevacizumab or aflibercept who are able to be seen every one or two months will remain on anti-VEGF therapy, but those patients who have transportation issues, a strong preference for reduced injections or with minimal pressure response to IVTA or Ozurdex will be the most likely candidates for fluocinolone acetonide. When considering the three-year efficacy of fluocinolone acetonide, it is important to remember that patients still need frequent follow-up to check IOP. With regard to side effects, we largely discount cataract formation, given that most DME patients will have early visually significant cataracts regardless of treatment with steroid and that modern cataract surgery is very

safe and effective. Glaucoma, however, is an important consideration in any patient for whom corticosteroid treatment for DME is considered. In conclusion, steroids are an important second-line treatment in the retinal physician’s armamentarium for DME. Today’s formulations of intravitreal steroid allow the clinician to select shorter-acting or sustainedrelease preparations tailored to the individual patient’s needs.

REFERENCES: 1. R. Varma et al. JAMA Ophthalmol. 2014: 132(11): 1334-1340. 2. H. Tamura et al. Invest. Ophthalmol. Vis. Sci. 2005; 46(4): 1440-1444. 3. E.A. Felinski and D.A. Antonetti. Curr. Eye Res. 2005; 30(11): 949-957. 4. J.L. Edelman, D. Lutz D and M.R. Castro. Exp. Eye Res. 2005: 80(2): 249-258. 5. X. Zhang et al. Diabetes 2008; 57(4): 1026-1033. 6. M.C. Gilles et al. Ophthalmology 2006; 113: 1533-1538. 7. M.H. Dehghan et al. Int. Ophthalmol. 2008; 28: 7-17. 8. M.S. Ip et al. Retina 2008; 28: 919-930. 9. T. Yilmaz et al. Ophthalmology 2009; 116: 902-911. 10. M.J. Elman et al. Ophthalmology 2010; 117: 1064–1077. 11. M.J. Elman et al. Ophthalmology 2011; 118: 609-614. 12. E. Jin et al. Ann. Pharmacother. 2015: 49(4): 387-397. 13. A. Watanabe et al. J. Ocul. Pharmacol. Ther. 2015. 14. D.S. Boyer et al. Ophthalmology 2014; 121(10): 1904-1914. 15. A.J. Augustin et al. BMC Ophthalmol. 2015; 15(1): 150. 16. P.A. Campochiaro et al. Ophthalmology 2011; 118: 626-635. 17. P.A. Campochiaro et al. Ophthalmology 2012; 119(10): 2125-2132. 18. P.A. Pearson et al., Ophthalmology 2011; 118(8): 1580-1587. 19. Q.D. Nguyen et al. Ophthalmology 2012; 119(4): 789-801.

DR MARGARET A. GREVEN E: margaret.greven@gmail.com DR. PETER KARTH E: peterkarth@gmail.com MARCH 2016 :: Ophthalmology Times Europe

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Progressive approaches in retina Outer retinal layer thickness predicts visual acuity in diabetic macular oedema A common health problem in developed countries is diabetes mellitus with diabetic macular oedema (DMO). This major cause of visual loss is explored here, as well as areas for future studies. By Charlotte Lindsay Reviewed by Dr Ian Wong

Diabetes mellitus is a common health problem in developed countries, with diabetic macular oedema (DMO) being a major cause of visual loss.1 A variety of treatment modalities for DMO are available including laser, steroid and intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents.2-6

Evaluating DMO with OCT scans Over the past 10 years, optical coherence tomography (OCT) scans have been used to provide a quantitative assessment of DMO and to evaluate the efficacy of treatment as it provides a fast, objective and non-invasive way of detecting structural changes.7 The correlation between visual acuity and OCTmeasured variables, however, has not yet been well established. Some reports of OCT-measured macular changes show a correlation with

ORL thickness should be a better prognostic measurement of vision than total retinal thickness because it was not affected by the amount of cystoid oedema in the outer plexiform layer and subretinal fluid. vision, but several studies have had conflicting results.7-11 Retinal microstructures can now be seen, as advances in OCT technologies have led to faster scanning and higher axial resolution. Therefore, we can study morphological changes in the outer retinal hyper-reflective bands, specifically the inner segment/outer segment (IS/OS) junction, and measure the length of the photoreceptor outer segment (PROS). Both IS/OS integrity and PROS length have been reported to be indicators of visual acuity in DMO and other diseases. 12-13 Forooghian et al measured the distance between the IS/OS junction and RPE layer to

IN SHORT

(FIGURE 1) Fundus photography showing diabetic macular oedema. (Photo courtesy of Dr Ian Wong)

www.oteurope.com

ORL thickness appears to have a better correlation with vision than CFP thickness in DMO. Further studies are warranted to investigate the use of ORL thickness as a prognostic factor of vision in diabetic macular oedema patients.

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(FIGURE 2) Spectral-domain optical coherence tomography scan showing the measurement of central foveal point (CFP) thickness and outer retinal layer (ORL) thickness. ELM, external limiting membrane. IS/OS, inner segment/outer segment junction. COST, cone outer segment tips. RPE, retinal pigment epithelium. (Photo courtesy of Dr Ian Wong)

approximate the PROS length and showed that vision correlated better with PROS length than with macular thickness in DMO.13 The inner segment of photoreceptor, however, is also important for vision because it contains mitochondria and provides energy for the phototransduction process. A study was therefore designed to measure the distance between the retinal pigment epithelium (RPE) and ELM to approximate the length of inner and outer segments of photoreceptors, and to determine its correlation with visual acuity in patients with DMO.14

Methods Adults with evidence of DMO determined on OCT scan or slit lamp biomicroscopy, who attended the University of Hong Kong Eye Clinic during a 3-month period were recruited for the study.14 Spectralis spectral-domain OCT was used to assess the foveal structures and Heidelberg Explorer was used to analyse

Retinal microstructures can now be seen, as advances in OCT technologies have led to faster scanning and higher axial resolution. data captured. The ELM, RPE and internal limiting membrane (ILM) were manually set. The brightest point of ELM and RPE at the foveal centre was used as the reference point for measurement of thickness. The central foveal point (CFP) thickness was measured as the distance between the ILM and RPE, and the outer retinal layer (ORL) thickness was measured as the distance between ELM and RPE at the foveal centre. Patients were excluded if there was ELM disruption or RPE segmentation.

Results14 Of the 78 patients recruited, the mean age of patients was 58.1 years and the mean visual

acuity was 20/40. The mean CFP thickness was 398 μm and the mean ORL thickness was 115.7 μm. The correlation coefficient and square of the correlation coefficient between the CFP thickness and Snellen visual acuity were 0.34 and 0.12 respectively (P<0.001). The correlation coefficient and square of the correlation coefficient between ORL thickness and Snellen visual acuity was −0.65 and 0.42 respectively (P<0.001).

Correlation between central retinal thickness and vision The correlations between central retinal thickness and visual acuity have been reported in many studies but the results varied and different measurements were used in different studies.7-11 In this study14, ORL thickness was defined as the distance between ELM and RPE, which is the sum of the inner and outer segments of photoreceptors. Both segments are important for vision: the inner segment contains mitochondria MARCH 2016 :: Ophthalmology Times Europe

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Progressive approaches in retina In conclusion, ORL thickness appeared to have a better correlation with vision than CFP thickness in DMO.

thickness instead. Therefore, direct comparison of this study result with that of other studies is difficult. In addition, this study did not assess parameters contributing to vision other than photoreceptor health such as perfusion status and amount of macular ischaemia.

Conclusion and provides energy, whereas the outer segment contains discs with opsin that absorb photons for phototransduction. Decrease in ORL thickness therefore reflected damage to photoreceptors and decrease in visual function. ORL thickness should be a better prognostic measurement of vision than total retinal thickness because it was not affected by the amount of cystoid oedema in the outer plexiform layer and subretinal fluid. When the cystoid oedema and subretinal fluid resolve after treatment, the total retinal thickness would return to normal but damage to photoreceptors remains, leading to decrease in ORL thickness. This study revealed a high correlation between ORL thickness and visual acuity i.e. thicker ORL was associated with better vision. 14 This correlation was stronger than that between total retinal thickness at foveal centre and visual acuity. 14

Limitations and further research This study14 was limited to patients who had DMO without ELM disruption or RPE segmentation on OCT scans. The result is therefore not applicable to patients whose DMO is severe and associated with ELM or RPE damage. It should be noted that most studies in the literature used central subfield thickness to assess foveal thickness whereas this study used CFP www.oteurope.com

In conclusion, ORL thickness appeared to have a better correlation with vision than CFP thickness in DMO. Further studies are warranted to investigate the use of ORL thickness as a prognostic factor of vision in DMO patients.

REFERENCES 1. Kempen JH, O’Colmain BJ, Leske MC, Haffner SM, Klein R, Moss SE, Taylor HR, Hamman RF; Eye Diseases Prevalence Research Group. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol. 2004;122:552-63. 2. Early Treatment Diabetic Retinopathy Study Research Group. Focal photocoagulation treatment of diabetic macular edema. Relationship of treatment effect to fluorescein angiographic and other retinal characteristics at baseline: ETDRS report no. 19. Arch Ophthalmol. 1995;113:1144-55. 3. Diabetic Retinopathy Clinical Research Network (DRCR.net), Beck RW, Edwards AR, Aiello LP, Bressler NM, Ferris F, Glassman AR, Hartnett E, Ip MS, Kim JE, Kollman C. Threeyear follow-up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol. 2009;127:245-51. 4. Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, Gibson A, Sy J, Rundle AC, Hopkins JJ, Rubio RG, Ehrlich JS; RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119:789-801. 5. Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL 3rd, Friedman SM, Glassman AR, Scott IU, Stockdale CR, Sun JK; Diabetic Retinopathy Clinical Research Network. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2011;118:609-14. 6. Brown DM, Schmidt-Erfurth U, Do DV, Holz FG, Boyer DS, Midena E, Heier JS, Terasaki H, Kaiser PK, Marcus DM, Nguyen QD, Jaffe GJ, Slakter JS, Simader C, Soo Y, Schmelter T,

Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Zeitz O, Metzig C, Korobelnik JF. Intravitreal Aflibercept for Diabetic Macular Edema: 100-Week Results From the VISTA and VIVID Studies. Ophthalmology. 2015;122:2044-52. 7. Baskin DE. Optical coherence tomography in diabetic macular edema. Curr Opin Ophthalmol. 2010;21:172-7. 8. Kim BY, Smith SD, Kaiser PK. Optical coherence tomographic patterns of diabetic macular edema. Am J Ophthalmol. 2006;142:405-12. 9. Diabetic Retinopathy Clinical Research Network, Browning DJ, Glassman AR, Aiello LP, Beck RW, Brown DM, Fong DS, Bressler NM, Danis RP, Kinyoun JL, Nguyen QD, Bhavsar AR, Gottlieb J, Pieramici DJ, Rauser ME, Apte RS, Lim JI, Miskala PH. Relationship between optical coherence tomography-measured central retinal thickness and visual acuity in diabetic macular edema. Ophthalmology. 2007;114:525-36. 10. Koleva-Georgieva D, Sivkova N. Assessment of serous macular detachment in eyes with diabetic macular edema by use of spectraldomain optical coherence tomography. Graefes Arch Clin Exp Ophthalmol. 2009;247:1461-9. 11. Murakami T, Yoshimura N. Structural changes in individual retinal layers in diabetic macular edema. J Diabetes Res. 2013;2013:920713. 12. Wong IY, Iu LP, Koizumi H, Lai WW. The inner segment/outer segment junction: what have we learnt so far? Curr Opin Ophthalmol. 2012;23:210-8. 13. Forooghian F, Stetson PF, Meyer SA, Chew EY, Wong WT, Cukras C, Meyerle CB, Ferris FL 3rd. Relationship between photoreceptor outer segment length and visual acuity in diabetic macular edema. Retina. 2010;30:63-70. 14. Wong RL, Lee JW, Yau GS, Wong IY. Relationship between Outer Retinal Layers Thickness and Visual Acuity in Diabetic Macular Edema. Biomed Res Int. 2015;2015:981471.

CHARLOTTE LINDSAY E: charlottelindsay@hotmail.com Charlotte is a freelance writer IAN Y.H. WONG E: wongyhi@hku.hk Department of Ophthalmology, Queen Mary Hospital, Pokfulam, Hong Kong; Department of Ophthalmology; The University of Hong Kong; and the Research Centre of Heart, Brain, Hormone & Healthy Aging, LKS Faculty of Medicine, The University of Hong Kong.

The authors have no financial disclosures relating to the content of this article.

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Progressive approaches in retina Mixed results for neovascular AMD gene therapy In a Phase IIa study of patients with neovascular age-related macular degeneration, a single subretinal injection of rAAV.sFlt-1 gene therapy (AVA101) demonstrated acceptable safety, but not a complete or durable response. Additional preclinical research is underway. Cheryl Guttman Krader Reviewed by Jeffrey S. Heier, MD

n a phase II a study, rAAV.sFlt-1 gene therapy (AVA-101, Avalanche Biotechnologies) for neovascular age-related macular degeneration (AMD) demonstrated acceptable safety, but failed to provide a complete or durable anti- vascular endothelial growth factor (VEGF) response. The results are disappointing, but do not necessarily spell the end of the investigational product’s development, according to Jeffrey S. Heier, MD, director of the Vitreoretinal Service, Ophthalmic Consultants of Boston, MA. ‘I still believe gene therapy is well suited for the management of retinal disease. It has a proven track record in humans and, for a variety of reasons, the retina is ideally suited for developing gene-based therapies. Furthermore, there is a strong rationale for developing a sustained delivery product that could help with the ongoing treatment burden,’ commented Dr. Heier. ‘Numerous factors are being studied in an effort to fully understand the responses observed in the Phase IIa study of AVA-101, and more preclinical research is underway that will hopefully provide insight into the variables that can improve outcomes.’ AVA-101 uses an adeno-associated viral vector to deliver a gene that produces naturally occurring soluble VEGF receptor-1 (sFlt-1). The study enrolled patients with treatment-naive or previously treated neovascular AMD. In total, 32 patients were randomised 2:1 to receive a single subretinal injection of AVA-101 or control. All patients received an intravitreal injection of ranibizumab 0.5 mg (Lucentis; Genentech, San Francisco, CA) at day 0 and month 1. The genetherapy group underwent core vitrectomy and received the AVA-101 subretinal injection adjacent to the macula on day 7, and all patients returned

for monthly follow-up visits until week 52. During the course of the study, all patients were eligible for rescue treatment with ranibizumab, which was given as needed based on pre-specified retreatment criteria. At week 52, mean visual acuity increased from baseline by 2.2 letters in the AVA-101 group, while the control arm showed a mean loss of 9.3 letters. ‘There was a statistically significant difference between the treatment and control arms, but this was largely driven by poor performance in the control arm due to three subjects losing at least four lines of visual acuity from baseline,’ Dr. Heier said. Anatomic outcomes were better in the control arm. Centre point thickness (CPT) at one year showed a 27 micron increase from baseline in the AVA-101 arm but an 85 micron decrease from baseline in the control arm. There were no serious ocular adverse events associated with the investigational therapy and no systemic safety signals attributed to AVA-101. All patients in the AVA-101 arm who were phakic at baseline developed a cataract, and three AVA101 patients (14%) developed a moderate vitreous haemorrhage that was related to the sclerotomy or trocar insertion used for delivery.

IN SHORT According to Jeffrey S. Heier, MD, director of the Vitreoretinal Service, Ophthalmic Consultants of Boston, MA, mixed results do not necessarily spell the end of the investigational product’s development. Cheryl Guttman Krader reports.

MARCH 2016 :: Ophthalmology Times Europe

ISSUE FE ATURE

Progressive approaches in retina Lessons and questions Dr. Heier said that when results do not turn out as expected, it is necessary to go back to basics and try to understand the underlying reasons. He pointed out that there was significant variation in the number of rescue ranibizumab injections received by patients in the treatment arm. ‘For example, there may be something we can learn from determining why some patients received very few ranibizumab injections and others received many more,’ he said. Other issues being evaluated include whether the subretinal delivery route and the AAV vector itself are optimal – not all vectors are created equal, Dr. Heier said.

He also noted that the experience of this study underscores the challenges in conducting surgical treatment trials. ‘Surgical trials for treating medical diseases are extremely difficult to design,’ Dr. Heier said. Issues to consider pertain to patient selection criteria, what represents an appropriate sham control and masking of patients and examiners. Dr. Heier also made the point that it is difficult to implement the control arm of a surgical trial providing extended delivery treatment for neovascular AMD. Although standard of care today mandates anti-VEGF therapy for any level of fluid because it represents early disease

recurrence, subtle fluid may not be an indicator of disease recurrence in an eye treated with an extended delivery therapy. ‘Perhaps the latter patients are at less risk of vision loss when subtle fluid is seen,’ Dr. Heier said. In addition, a surgical approach introduces confounders that can be difficult to control for within a clinical trial. ‘It is much more difficult to control for differences in eyes in a surgical study than in a study of an intravitreal injection. There are also differences in surgeon skills and other issues to consider, such as where to place the bleb and how to manage cataracts,’ Dr. Heier explained.

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cataract & refractive Novel trifocal IOL extends range of vision Early results for visual acuity, contrast sensitivity, and photopic symptoms are encouraging By Cheryl Guttman Krader; Reviewed by Rudy M.M.A. Nuijts, MD, PhD, Soraya M.R. Jonker, MD, and Noël J.C. Bauer, MD, PhD

new non-apodized diffractive trifocal presbyopia-correcting IOL (AcrySof IQ PanOptix, Alcon Laboratories) is designed to bring patients a full and seamless range of uncorrected vision, including a wide range of comfortable near to intermediate vision (40 to 80 cm) with a crisp focal point at 60 cm. The new IOL was launched in Europe at the 2015 meeting of the European Society of Cataract and Refractive Surgeons (ESCRS) in Barcelona, Spain, and is not available in the United States. It features patented optical technology (ENLIGHTEN; ENhanced LIGHT ENergy) that redistributes the extended intermediate focal point (120 cm) to the distance focal point for an amplified performance. The

IN VIEW: The novel diffractive optic has two step heights, sends energy to three foci—near (40 cm), a preferred intermediate distance (60 cm) and far (infinity)—regardless of pupil size, and allows 88% energy utilization. (Image courtesy of Rudy M.M.A. Nuijts, MD, PhD)

novel diffractive optic has two step heights, sends energy to three foci—near (40 cm), a preferred intermediate distance (60 cm) and far (infinity)—regardless of pupil size, and allows 88% energy utilization. At the ESCRS Congress, Rudy M.M.A. Nuijts, MD, PhD, presented positive early clinical outcomes for a small series of patients with the new trifocal IOL implanted at the University Eye Clinic Maastricht, the Netherlands. Dr. Nuijts and his colleagues, Soraya M.R. Jonker, MD, and Noël J.C. Bauer, MD, PhD, analyzed the outcomes and put them into perspective by comparing them with historical control groups implanted with another trifocal multifocal IOL (Fine Vision Micro F, Physiol) or a +3.0 D bifocal multifocal IOL (AcrySof IQ ReSTOR +3.0, Alcon Laboratories). The historical data were from a randomized clinical trial conducted by the same group at the University Eye Clinic Maastricht [Jonker SM, et al. J Cataract Refract Surg. 2015;41:1631-1640]. “At 1 month after surgery, we found that the new trifocal IOL was associated with very good monocular distance corrected visual acuity, and it provided uncorrected and distance corrected intermediate and near visual acuity that compared well to the historical controls,” said Dr. Nuijts, professor of ophthalmology, University Eye Clinic Maastricht, The Netherlands. “Furthermore, the binocular defocus curve of the new trifocal IOL showed a more continuous range with a probable best intermediate visual acuity of around 50 to 60 cm.” In addition, contrast sensitivity testing performed in the first group of eyes with the trifocal IOL implanted showed excellent results under photopic and mesopic conditions that were superior to those of the historical controls and even when compared with an age-related phakic control group, he noted. MARCH 2016 :: Ophthalmology Times Europe

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“Furthermore, the new IOL seemed to be associated with fewer patient complaints of bothersome glare than the other presbyopia-correcting IOLs,” Dr. Nuijts said.

About the case series

NEW JENVIS Dry Eye Report RUDY M.M.A. NUIJTS, MD, PHD E: rudy.nuijts@mumc.nl Dr. Nuijts is a consultant to Alcon Laboratories and receives lecture fees and study grant support from Alcon. He is a consultant to Thea Pharma and ASICO, and received study grants from AcuFocus, Alcon Surgical, Carl Zeiss Meditec, Ophtec, and Physiol. SORAYA M.R. JONKER, MD E: soraya.jonker@mumc.nl Dr. Jonker has no financial or proprietary interest in any material or method mentioned. NOËL J.C. BAUER, MD, PHD E: n.bauer@mumc.nl Dr. Bauer received study grants from Alcon Laboratories, Carl Zeiss Meditec, and Physiol and a lecture fee from Alcon Surgical. www.oteurope.com

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The series with the new trifocal IOL implanted included 16 eyes of 9 patients. The patients had a mean age of about 60 years, mean preoperative corrected distance visual acuity was 0.14 ± 0.24 logMAR, and mean preoperative SE was –0.56 ± 1.71 D. The defocus curve and distance visual acuity measurements were performed with the ETDRS chart, near and intermediate visual acuity measurements were done using the ETDRS near vision chart, and contrast sensitivity was evaluated using the CSV-1000 (VectorVision). Visual acuity results for the two historical control groups were based on testing performed at 6 months after surgery, and binocular defocus curve and contrast sensitivity testing for the controls was done at 3 months after surgery. The refractive outcomes in eyes with the new trifocal IOL implanted were very good—mean SE at 1 month after surgery was ¬0.04 ± 0.45 D. Mean logMAR values for uncorrected distance, intermediate, and near visual acuity were 0.15 ± 0.14, 0.23 ± 0.14, and 0.28 ± 0.14, respectively; mean distance corrected distance, intermediate, and near visual acuity were –0.02 ± 0.15, 0.24 ± 0.17, and 0.18 ± 0.15, respectively. In defocus testing, the new IOL provided visual acuity of 0.2 logMAR or better from +1.0 D to –3.0 D defocus. While the two historical presbyopiacorrecting IOLs also provided a good range of vision, the results with the PanOptix IOL were more continuous with the new trifocal.

cataract & refractive Are extended-depth-of-focus IOLs hitting the visual sweet spot? Designs of current IOLs provide myriad optical options for the correction of presbyopia. Regardless of the principal of correction, compromise is required. However, a new class of IOLs, currently referred to as extended-depth-of-focus IOLs (EDOF-IOLs), seems to be generating very satisfied patients. Dr. Robert T. Ang Reviewed by Professor Sunil Shah

urrent IOL designs offer a variety of optical options for the correction of presbyopia. Regardless of the principal of correction, compromise is required. However, a new class of IOLs, currently referred to as extended-depth-of-focus IOLs (EDOF-IOLs), seems to be generating very satisfied patients. I categorise presbyopia-correcting IOLs into three categories: multifocal, accommodating and EDOF-IOLs. The multifocal category encompasses diffractive optic lenses that split light between distance, intermediate and near. The user can focus on only one distance at a time, leaving the blur from the other focal points to sometimes cause halo and glare. The accommodating IOL needs either forwardbackward axial movement or flexibility in lens shape or thickness to effect change in focal point from distance to near vision. However, capsular fibrosis can impact the presbyopiacorrecting capability and induce asymmetric vaulting, leading to lens tilt. This makes the currently available accommodating IOL challenging to handle at times. Although premium multifocal lenses offer patients good results, market penetration of these lenses has remained relatively low, at 7.2% of cataract surgeries. In fact, monovision with standard IOLs is nearly three times more common than IOLs offering presbyopia correction,1 most likely because of the shortcomings associated with multifocal IOLs, such as glare and halos. The EDOF class of IOL is an emerging technology that employs new methods to improve the range of vision without splitting light rays. The goal of the EDOF-IOL is to address patient expectations and demand for

â&#x20AC;&#x153;I categorise presbyopia-correcting IOLs into three categories: multifocal, accommodating and EDOF-IOLs.â&#x20AC;? presbyopia correction without compromising functional vision across all distances. As opposed to the single focal point of monofocal lenses or two distinct foci for multifocal lenses, an EDOF-IOL smooths out the dips in the defocus curve by creating one elongated focal point. There are currently three different lenses that can be classified as EDOF-IOLs, which employ radically different technology.

Small aperture design Based on the KAMRA corneal inlay (AcuFocus, Inc., United States) technology, the IC-8 lens (AcuFocus, Inc., United States) features an embedded opaque annular mask that blocks unfocused peripheral light rays while allowing paraxial light rays through its central aperture.

IN SHORT This article explores a new class of IOLs, currently referred to as extended-depth-offocus IOLs (EDOF-IOLs), which seem to be generating very satisfied patients. Designs offer a variety of optical options for the correction of presbyopia.

MARCH 2016 :: Ophthalmology Times Europe

(FIGURE 1) The IC-8 IOL has received CE Mark and is currently under post-market clinical evaluation in a number of clinics globally. (Image courtesy of AcuFocus)

“Technicians reported that ocular assessments were successful and required no different instructions for eyes with the IC-8 IOL.” The small aperture design creates an extended, continuous range of functional vision across all distances and is much more forgiving to a missed target refraction. Clinical trials demonstrated a mean visual acuity of 20/20 at distance and intermediate, with 100% of patients achieving 20/25 targetcorrected intermediate visual acuity and target-corrected distance visual acuity.8 When combined with –0.75 D of myopia, patients can achieve the equivalent of 2.25 D of add power across an extended range of vision. Not only does this allow for natural visual adjustment, but the mask embedded in the IOL does not decrease binocular contrast sensitivity even under mesopic conditions. 2 In my experience, the lens is well tolerated, with patients reporting similar visual symptoms to those in their untreated fellow eye. www.oteurope.com

Imaging through the IOL mask’s central aperture is possible, with minimal differences noted between the IC-8 IOL and fellow eyes with an implanted monofocal IOL.9 Technicians reported that ocular assessments were successful and required no different instructions for eyes with the IC-8 IOL. Vitreoretinal surgery in eyes implanted with the IC-8 IOL can be performed with ease and good visibility,10, 11 making the IC-8 IOL suitable for ametropic, emmetropic and post-LASIK presbyopes, as well as monofocal pseudophakic patients. The IC-8 IOL has received CE Mark approval and is available in select European markets. It has not been approved for use in the United States.

Echelette The proprietary echelette design of the TECNIS Symfony IOL (Abbott Medical Optics, Inc.) forms a step structure whose blaze angle elongates the focus of the eye to produce an extended range of vision. 3 This enhanced design is combined with achromatic technology that corrects longitudinal chromatic aberrations. This results in sharper focus of light and increased contrast sensitivity. When combined with correction of spherical aberration, it increases retinal image quality

cataract & refractive Clinical studies indicate that the lens maintains its transparency for up to seven years following implantation. The registry recorded nearly 1.0 for uncorrected distance visual acuity, J1+ for uncorrected intermediate visual acuity, on average, and near vision within the range of social reading for all patients (mean uncorrected near visual acuity J2.6). Patient satisfaction is high, with only 4% of patients reporting optical phenomena such as halo/ glare. Ninety-three per cent of patients report near spectacle independence and 89% were satisfied with their outcome.7 The WIOL-CF is currently under evaluation in Europe, Mexico and parts of Asia. It has not been approved for use in the United States. (FIGURE 2) The IC-8 lens features an embedded opaque annular mask that blocks unfocused peripheral light rays while allowing paraxial light rays through its central aperture. (Image courtesy of Dr. Robert Ang, MD)

without negatively affecting depth of focus.4,5 Studies conducted on the Symfony IOL showed sustained mean visual acuity of 20/20 or better at distance and intermediate, sustained through 1.5 D of defocus, and a 1.0 D increase in range of vision throughout the defocus curve.6 In one study, 97% of 31 subjects implanted with the Symfony IOL indicated that they would elect to have the lens implanted again.6 The Symfony has received the EU Mark of approval and is available in select European and Asian countries. It has not been approved for use in the United States.

Bioanalogic IOL Unique in its design and use of materials is the WIOL-CF (Medicem) polyfocal IOL.

“The Symfony has received the EU Mark of approval and is available in select European and Asian countries.” Produced from a proprietary hydrogel designed to mimic the properties of the natural young crystalline lens, the clear lens enables polyfocal accommodation within a continuous range from near to distant focus. Multicentre observational registry database studies indicated excellent visual acuity for far and intermediate vision, and contrast sensitivity exceeding population norms under all light conditions.

Making the most of EDOF-IOLs Because the EDOF-IOL does not split light, patients experience less glare and halos; however, the intensity of near vision does not match that provided by a multifocal lens. To compensate for the decrease in near vision in patients implanted with an EDOF-IOL, I often use a minimonovision strategy, targeting one eye for distance and the other for slight myopia of –0.75 to –1.0. This gives good near vision, and the decrease in far vision from the low myopia is not as pronounced as the decreased contrast experienced by patients who are implanted with a multifocal IOL. Typically, patient complaints for the multifocal IOLs are centred on quality of vision: far vision is not sharp enough or they may experience decreased contrast, glare or halos. Contrast sensitivity testing in EDOF-IOLs demonstrates that, MARCH 2016 :: Ophthalmology Times Europe

when the range of vision is extended, there is a slight decrease in contrast compared with a plain monofocal lens, but it is much better than that experienced with a multifocal lens. Most patients feel that this slight lack of contrast sensitivity is more than compensated by the extended range of vision possible. The EDOF-IOLs are also available to patients deemed unsuitable for multifocal lenses, such as those who have had previous LASIK surgery or those with diabetic retinopathy or glaucoma.

Conclusion The emerging EDOF-IOL category of lenses has the potential to change presbyopia correction. In addition to taming the issue of halos and glare associated with multifocal lenses, these products offer exciting options to the patient previously excluded from the multifocal demographic. I expect the ongoing studies to further demonstrate the efficacy and versatility of these lenses, making limited spectacle dependence a possibility for a large population of patients.

REFERENCES 1. ASCRS Clinical Survey. Eyeworld. http://eyeworld.org/ supplements/2014_ASCRS_clinical_survey.pdf [Accessed December 20, 2014]. 2. S. Manzanera et al., Presented at ESCRS, London, 2014. 3. TECNISÂŽ Symfony DFU. 4. H.A. Weeber and P.A. Piers. J. Refract. Surg. 2012; 28(1): 48-52. 5. P. Artal et al., Opt. Express 2010; 18(2): 1637-1648. 6. 166 Data on file. Extended range of vision IOL 3-month study results (NZ). 7. D. Sivekova et al., ESCRS, Amsterdam, 2013. 8. Data courtesy of Robert Ang, MD 9. Data courtesy of Amadeo Veloso, MD. 10. Results from an animal study conducted by Dr Barry Kupperman, professor of ophthalmology and biomedical engineering; chief, Retina Service; vice-chair, Clinical Research, Ophthalmology at UC Irvine School of Medicine. 11. Personal experience in one patient from Professor Burkhardt Dick, MD.

Ophthalmology Times Europe is a comprehensive publication covering all of the latest developments within the ophthalmic industry with a broad focus on cataract, corneal and refractive surgery, as well as glaucoma and vitreoretinal conditions.

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www.oteurope.com/enewssignup ROBERT T. ANG, MD E: rtang@asianeyeinstitute.com Robert T. Ang, MD, specialises in cornea and refractive surgery, glaucoma, and comprehensive ophthalmology at the Asian Eye Institute, located in the Philippines. www.oteurope.com

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cataract & refractive Clinical experience with a mechanical pupil dilator for challenging cases Small pupils in cataract surgery patients present a particular challenge for surgeons. Using a pupil expansion device, such as the Malyugin ring, may help to reduce the complications associated with small pupil cataract surgery. Cedric Schweitzer, MD Reviewed by Jorge Alio

ataract surgery in patients with small pupils is associated with a raft of complications including damage to and prolapse of the iris into a wound, the creation of a small anterior capsulorrhexis (leading to anterior capsule damage), incomplete removal of the cortical material, postoperative inflammation and a higher risk of posterior capsule rupture.1,2 A small pupil also hampers visualisation of the peripheral capsule, making it difficult to ensure that the lens and haptics are placed completely in the bag. Achieving and maintaining adequate mydriasis is crucial in preventing serious complications. However, we are fortunate to have more interventions and instruments available than ever before to help us deal with these difficult cases.

â&#x20AC;&#x153;The brainchild of Boris Malyugin, the Malyugin ring was designed to overcome a myraid of disadvantages.â&#x20AC;? Managing small pupil size There are a number of options for increasing pupil size, including the use of intracameral mydriatics such as Shugarcaine and epi-Shugarcaine, viscodilatation and pupil-expansion devices. The pupil-expansion devices available include plastic and metal iris hooks, Clarke and Siepser rings, the Graether expander (Eagle Vision Inc.), the 5S iris ring (Morcher GmbH) and Perfect Pupil (Milvella Pty Ld), to name a few. I nearly always used iris hooks in patients with small pupils. However, for my difficult cases, including patients with intraoperative floppy iris syndrome and pseudoexfoliation syndrome, I now almost always use the Malyugin ring (MicroSurgical Technology, Inc.). The brainchild of Boris Malyugin, professor of ophthalmology and deputy director general at the S. Fyodorov Eye Microsurgery State Institution in Russia, the Malyugin ring was designed to overcome some of the disadvantages associated with other pupil expanders, such as overstretching of the iris sphincter and extended surgery time. The Malyugin ring is a square-shaped device made from

IN SHORT

(FIGURE 1) (Photo courtesy of MicroSurgical Technologies)

The Malyugin ring was designed to overcome some of disadvantages associated with other pupil expanders such as local overstretching of the iris sphincter and the need to perform additional corneal incisions

MARCH 2016 :: Ophthalmology Times Europe

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cataract & refractive Technology, Redmond, WA), which is designed for the specific geometry of the Malyugin ring, through a second incision. After surgery, the same Osher micromanipulator can be used to remove the twelve oâ&#x20AC;&#x2122;clock scroll, while the injector can be used to quickly and smoothly remove the ring without trauma to the iris sphincter (Figure 2). Unlike other pupil-expansion devices, the injector can be disposed of once surgery is complete, eliminating the need for sterilisation and its associated costs.

Additional tools

(FIGURE 2) (Photo courtesy of MicroSurgical Technologies)

5/0 polypropylene with a paperclipscroll design that holds the iris at eight equidistant points. The result is a round pupil, rather than the square one formed with four iris hooks, and circumferential protection of the iris (Figure 1). The device is available in two sizes, 6.25 mm and 7.00 mm, which offers a degree of flexibility. For example, while the 6.25 mm ring is suitable for most cases, the 7.00 mm ring is more suitable when placing an IOL with a large-diameter optic, or for surgeons who use the divide-and-conquer technique.

Key advantages of the Malyugin ring I used to employ iris hooks during cataract surgery in patients with small pupils. In doing so, it was necessary for me to create four or five corneal incisions. Although I never experienced any problems with hooks, there is the risk that they might overstretch the iris sphincter and create iris defects. The main advantage of the Malyugin ring is that

it can be inserted via the main clear corneal incision, eliminating the need for multiple incisions. There is no need to widen the main incision. I use a 2.2 mm incision and can easily place the Malyugin ring through it. This obviously saves considerable surgical time and is less invasive than using iris hooks. The Malyugin ring also eliminates stretching or distorting of the pupil. Because it affords minimal contact with the iris, it is less likely to damage the iris sphincter than other rings or hooks. Perhaps not surprisingly, I no longer turn to hooks when I need to perform mechanical pupil expansion. The Malyugin ring is very easy to use thanks to its disposable injector, which aids placement of the ring around the edge of the pupil. Typically, the first three of the four paperclip-like scrolls are very easy to insert. However, to facilitate insertion of the fourth scroll close to the main incision, I would advise using the injector and an Osher micromanipulator (MicroSurgical

I also use other pupil expanders and hooks, although perhaps less frequently than the Malyugin ring. Alcon iris hooks (Alcon Laboratories) are useful in specific cases where I need to open the iris locally rather than globally. In cases of traumatic damage, some local pupillary defect or iris desinsertion may happen and iris hooks help ensure safer cataract surgery. Thankfully, small pupils are not very common so, for most surgeons, the need for hooks and mechanical dilators such as the Malyugin ring is somewhat limited. However, to date and in my experience, the use of the Malyugin ring appears to be safe without any intraoperative difficulties or complications observed. It undoubtedly provides greater confidence to the surgeon in offering safer and more effective cataract surgery to patients with small pupils.

REFERENCES 1. J.D. Bartlett and K.M. Miller. Compr. Ophthalmol. Update 2003; 4: 171-176. 2. Malyugin B. Cataract Refr. Surg. Today Europe. 2013: 26-30.

CEDRIC SCHWEITZER E: cedric.schweitzer@chu-bordeaux.fr Cedric Schweitzer, MD, is an ophthalmologist based at the University Hospital Bordeaux in France. Dr Schweitzer has no financial interests in MicroSurgical Technology, Inc. MARCH 2016 :: Ophthalmology Times Europe

cataract & refractive Adjustable intraocular lenses after cataract surgery Incorrect IOL power is one of the most frequent reasons for IOL exchange following cataract surgery. Different options for the correction of residual refractive errors are being developed, including piggyback IOLs, light-adjustable lenses and multicomponent IOLs. By Dr Dimitra M. Portaliou, PhD, FEBOphth; Reviewed by Alessandro Franchini

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ataract surgery is considered very effective for the restoration of precise visual acuity. The refinement of current surgical techniques, paired with technological advancements in IOL design and biometry methodology, has increased the accuracy of IOL power calculations, minimising refractive surprises following cataract surgery. Nevertheless, it has been established that no cataract or refractive surgery will ever be 100% accurate due to errors in biometry, pre-existing or induced astigmatism, previous corneal refractive surgery, effective lens position and variables associated with wound healing.1 Most clinical studies report mean errors in IOL power calculation of approximately 0.50 D, with a standard deviation of 0.50 D or higher. Errors higher than 3 D are extremely rare but do occur,1–5 especially post refractive surgery. In this latter subgroup of patients, despite the use of special formulas for the IOL calculation,6 residual refractive errors are a frequent occurrence. In general, refractive surprises after cataract surgery can compromise an otherwise successful result by creating unsatisfactory visual acuity outcomes and can create situations that are difficult to handle for both patient and physician. Corneal-based procedures (laser refractive surgery) and lens-based procedures are commonly used in order to resolve the issue of poor refractive results following cataract surgery. However, corneal refractive surgery has several limitations: it is not suitable for high refractive errors and requires access to an Excimer laser, which may not always be available. Additionally, patient acceptance of new IOLs (e.g., multifocal) may require lens exchange where laser procedures would not be helpful. Finally,

dry eye symptoms can be created/exacerbated with corneal laser surgery, creating yet another challenge for both patient and physician. These problems are easily solved with multicomponent or piggyback IOLs. Lens-based procedures include IOL exchange, piggyback IOLs, light-adjustable lenses and multicomponent IOLs.

Lens-based procedures Lens-based procedures have significant advantages in certain situations.7 In particular, lens-based procedures are more suitable for the correction of high ametropias: 1) they are tissue-saving techniques, and 2) no corneal aberrations are induced; the corneal surface remains intact and the original cataract wounds can be used, avoiding additional unpredictable wound-induced astigmatism.

IOL exchange In IOL exchange, the incorrect lens is removed and replaced by a new lens inserted through the same incision. IOL exchange can be difficult (e.g., removing the primary lens from the capsular bag) due to progressive capsular bag shrinkage. Complications such as capsular tear, vitreous loss, retinal tears and macular oedema can occur,8 which

IN SHORT IOL exchange following cataract surgery can be difficult and lead to complications. Piggyback IOLs, light-adjustable lenses and multicomponent IOLs offer different options for the correction of residual refractive errors.

cataract & refractive

(FIGURE 1) Illustration of the MC-IOL in Vivo. (Photo courtesy of Dimitra M. Portaliou MD)

can permanently compromise the final refractive result. Lens exchange becomes an even bigger challenge once posterior laser capsulotomy has been performed.

Piggyback IOLs In 1993, Gayton and Sanders9 first described the piggyback IOL technique to provide adequate power in highly hyperopic patients. The technique involves the implantation of two IOLs in the posterior chamber of the same eye. The technique has been successfully expanded to address pseudophakic refractive error in normal eyes and eyes that have undergone penetrating keratoplasty. Piggyback implantation has been combined with the use of newly available minus-power lenses to provide appropriate power for cataract patients with keratoconus, as well as to correct pseudophakic myopia.10,11 Different designs with very promising results have been reported.11

Interlenticular fibrosis (ILF) with resultant hyperopic shift, opacification and loss of vision has become a concern linked with piggyback IOL implantation.11 There are some additional limitations; for example, if both lenses are placed in the bag, lens exchange is difficult. If one lens is in the bag and one in the sulcus, exchange of the sulcus lens is easier, but rotational stability and optical alignment are ongoing concerns.

Light-adjustable lenses Light-adjustable IOLs can correct the remaining refractive errors after cataract surgery. Appropriate spatial light intensity patterns are used to irradiate the IOLs and modify their shape after implantation, allowing the correction of spherical errors as well as astigmatism.12,13 Clinical studies have demonstrated that, after cataract surgery, light-adjustable IOLs irradiated with the appropriate spatial patterns can successfully correct

residual myopia, hyperopia and astigmatism.12,13 However, the behaviour of lightadjustable IOLs in the human eye and the accuracy of the corrections are still under investigation. There are several problems with the concept, which is still evolving. Firstly, the lens has to be sheltered from UV light prior to the final adjustment, which means that the patient must be protected from UV light for an indeterminate time. The refractive results of the IOL implant can change over a period of several weeks, perhaps months, depending on the nature of capsular contraction. Therefore, these lenses may have to be light adjusted then frozen prior to the final refractive stability in the eye. The advantage of this lens system is that the adjustment or correction can be done without additional intraocular surgery and requires only exposure to UV light. Once the adjustment has been made, no further adjustments are possible. If longer term adjustments are required, for example in cases of intolerance to multifocal optics or development of macular pathology, IOL exchange remains the only option.

Multicomponent IOL Illustration of the MC-IOL in vivo. Courtesy of Dr Dimitra Portaliou The multicomponent intraocular lens (MC-IOL, PrecisightTM IOL, Infinite Vision Optics) is a lens system (two lenses, one front lens, one base lens) that enables customised correction of all degrees of sphere, cylinder and multifocality in the primary surgery, as well as giving the surgeon the possibility to fine tune and/or reverse the optical properties of the lens at any postoperative time point.14 Besides accuracy and adjustability, the MC-IOL concept has several additional advantages. The front and base lens haptics are MARCH 2016 :: Ophthalmology Times Europe

cataract & refractive angled in different directions, such that the capsulorrhexis is captured during the primary surgery between the two haptics, preventing lens rotation. This is critical for toric correcting. Because of the capture of the capsulorrhexis between the front and base lens haptics, the front lens remains in front of the rhexis, outside the capsule, facilitating front lens exchange. This adjustable IOL allows the initial refractive result to be fine tuned by exchanging one of the two optical elements of the lens implant, the front lens. Postoperative surgical adjustments can be performed in the short term in order to correct residual refractive errors. Additionally, because vision is dynamic, the MC-IOL allows for long-term adjustments for the management of refractive changes such as progressive against-the-rule astigmatism (wound healing, age factors) and capsule contraction. Undesirable optics can easily be exchanged, for instance in cases of multifocal intolerance. Optical adjustments are often desirable years after the primary surgery, perhaps on development of agerelated macular degeneration. Finally, the multicomponent lens can be used for paediatric patients, in whom the eye’s growth causes progressive refractive change over time.15 All such lens-exchange surgical procedures are performed in a fraction of the time required for full lens exchange.

From a surgeon’s perspective From a surgeon’s perspective, such a multicomponent IOL offers a customised prescription to patients at the time of the primary surgery; utilising a small inventory of lens components minimises the need for secondary touchups as well as offering adjustability at any postoperative time point. www.oteurope.com

A feasibility study conducted with the MC-IOL, previously reported, described the two-year follow up after implantation in six patients.14 Previous studies of piggyback lens systems have demonstrated problems related to ILF, fibrotic membranes that develop between the two piggybacked lenses.11 Unlike these previous lens implantations, which placed both lenses in the capsular bag, the MC-IOL optically integrated dual lens system places the base lens in the bag while the front, piggyback, lens sits in front of the anterior capsule, outside the bag, thus avoiding ILF.14 Safe lens exchange can be performed even after posterior laser capsulotomy. The main disadvantage to this system is that a second intraocular surgery is required in some cases, if refractive adjustments are necessary. A new multicomponent IOL recently has entered the European market–the Harmoni Modular IOL from ClarVista, United States. The ClarVista system, with its unique modular design, offers visual correction of aphakia in patients following cataract surgery. The lens has one component that serves as a haptic-holding device to secure a second element, the optic. The design of the IOL is intended to enable safe and easy exchange of the optic component to reduce residual postoperative refractive error at the time of surgery or at 3 months postoperatively, which is similar to the MC-IOL concept. The Harmoni received CE mark in September 2015.

the percentage of patients who have undergone previous corneal refractive surgery grows; these patients are particularly desirable of spectacle independence. Different surgical options for the correction of residual refractive errors are currently or soon to be available, including piggyback IOLs, light-adjustable lenses and multicomponent IOLs.

REFERENCES 1. R. Connors III, P. Boseman III and R.J. Olson. J. Cataract Refract. Surg. 2002; 28: 235-238. 2. B. Kiss et al., J. Cataract Refract. Surg. 2002; 28: 230-234. 3. M.S. Rajan, I. Keilhorn and J.A. Bell. Eye 2002; 16: 552-556. 4. J. Narvaez et al.,J. Cataract Refract. Surg. 2006; 32: 2050-2053. 5. J.-K. Wang, C.-Y. Hu and S.-W. Chang. J. Cataract Refract. Surg. 2008; 34: 262267. 6. W. Haigis. J. Cataract Refract. Surg. 2008; 34: 1658-1663. 7. H.E. El Awady and A.A. Ghanem. Graefes Arch. Clin. Exp. Ophthalmol. 2013; 251: 1861-1866. 8. J.J. Jones, Y.J. Jones and G.J. Jin. Am. J. Ophthalmol. 2014, 157(1): 154-162. 9. J.L. Gayton and V.N. Sanders. J. Cataract Refract. Surg. 1993; 19: 776-777. 10. G. Kahraman and M. Amon. J. Cataract Refract. Surg. 2010; 36(7): 1090-1094. 11. R.E. Fenzl, J.P. Gills 3rd and J.P. Gills. Curr. Opin. Ophthalmol. 2000; 11(1): 73-76. 12. F.H. Hengerer, H.B. Dick and I. ConradHengerer. Ophthalmology 2011; 118: 2382-2388. 13. A. Chayet et al., Br. J. Ophthalmol. 2010; 94: 690-692. 14. D.M. Portaliou, M.A. Grentzelos and I.G. Pallikaris. J. Cataract Refract. Surg. 2013; 39(4): 578-584. 15. D.M. Portaliou, G.D. Kymionis and I.G. Pallikaris. J. Refract. Surg. 2014; 30(1): 62-66. 16. F. Sanchez Leon, D.M. Portaliou and I.G. Pallikaris. CRST 2015 Jan: 40-42. 17. R. Packard. CRST 2015 Jan: 37-39.

Conclusion Despite advances in cataract surgery and biometry, incorrect IOL power remains one of the most frequent reasons for IOL exchange. In the near future, there might be an increase in the frequency of incorrect power calculations as

DIMITRA M. PORTALIOU, MD E: mimi24279@gmail.com Dimitra M. Portaliou, MD, practices at the School of Health Sciences, Institute of Vision and Optics, in the University of Crete, Greece. He has no financial or proprietary interest in any materials or methods described herein.

glaucoma Redefining cyclophotocoagulation with modified laser delivery While traditional transscleral cyclophotocoagulation is effective at lowering IOP in patients with glaucoma, it has a high rate of side effects. The new MicroPulse system is effective and affordable with an excellent safety profile. Nathan M. Radcliffe, MD Reviewed by Jorge Alio

Radcliffe

ike most hypotensive medications that patients are commonly prescribed, cycloablation was first introduced to reduce IOP by decreasing the production of aqueous humour via the destruction of the ciliary epithelium. Over time, this treatment has evolved to transscleral cyclophotocoagulation (TSCPC) using a diode laser, which was found to produce the most targeted destruction in the ciliary epithelium. 1 While traditional TSCPC is effective at lowering IOP, it has also caused occasional cases of hypotony, phthisis and macular oedema. In a recent literature review, the incidence of hypotony (including phthisis) was found to be as high as 10%.2 While initially applied primarily to patients with recalcitrant glaucoma and few treatment options, TSCPC has gained in popularity in recent years. Studies show that TSCPC patients had final IOP results on par with tube and trabeculectomy patients, with fewer patients losing two or more lines of vision.3,4 TSCPC was found to be more effective than medical therapy at lowering IOP.5

MicroPulse laser therapy The development and recent FDA clearance of the new MicroPulse P3 glaucoma device (MP3; IRIDEX Corp.), powered by the new Cyclo G6 Glaucoma Laser System, has revolutionised cyclophotocoagulation using Iridex’s proprietary MicroPulse technology. First tested with retinal applications, multiple studies have shown MicroPulse TSCPC to be at least as effective as continuous-wave TSCPC, with fewer complications.6–8 MicroPulse programming takes a continuous wave of laser and breaks it into a series of repetitive pulses separated by pauses

that allow the tissue to cool, thus refraining from completely killing cells or causing damaging thermal build-up.9,10 I liken the technique to anti-lock brakes on a car. If you slam the brakes on, too much braking power can cause the wheel to freeze and the tyres to skid. Anti-lock brakes disseminate the braking power to prevent locking or skidding and ultimately stop the car safely, in a shorter distance. MicroPulse technology separates the laser delivery into a series of short pulses, controlling heat build-up and preventing thermal spread. As with continuous-wave TSCPC, the application of MicroPulse laser energy is guided by the probe. There may be some variability from one person to the next in terms of location of the pars plana and ciliary body; likewise, there is some variability of efficacy with both procedures. However, the application of MicroPulse to this traditional glaucoma laser therapy is showing very positive outcomes. Cyclophotocoagulation revolutionised – early clinical results Data were recently pooled from several institutions, including mine, to review 48 eyes from 45 patients.8 Following retrobulbar anaesthesia, each eye received two treatments of 50–90 s using the MP3 device with an 810 nm laser (Iridex). MicroPulse was set to a 31.3% duty cycle (0.5 ms treatment pulse followed by

IN SHORT MicroPulse transscleral cyclophotocoagulation is an effective, affordable and safe technique to lower IOP in patients with glaucoma.

MARCH 2016 :: Ophthalmology Times Europe

glaucoma

(FIGURE 1) (Photo courtesy of Dr Nathan Radcliffe)

1.1 ms of rest) and the eye was treated over the superior and inferior hemispheres, avoiding the temporal-most clock hour. Postoperative topical steroids were prescribed. At three months, we saw a mean reduction in IOP of 29.8% from baseline, which equals an average drop of 8.5 mmHg (P=0.027). The decrease in IOP was accompanied by a significant reduction in the number of ocular hypotensive medications the patients required, from a mean (standard deviation) of 3.3 (0.3) at baseline to 2.4 (0.3) at month three. There were no cases of visually significant hypotony, macular oedema or phthisis bulbi. Our results reinforced the findings of the previous prospective clinical study by Professor Paul Chew, MBBS, MMed(Ophth), FRCS(Ed), FRCOphth, FAMS, of the National University of Singapore. Professor Chewâ&#x20AC;&#x2122;s study demonstrated a reduction in IOP of more than www.oteurope.com

30% at 18 months, and the mean number of medications reduced from 2.1 to 1.3.11

The versatility of the MicroPulse P3 device One of the great benefits of the MP3 device is that it is incredibly versatile. The lower rate of complications demonstrated by Chew and others has led some of my colleagues and me to use this therapy earlier in the course of the disease than we would use continuous-wave TSCPC. It can be performed on an eye at any stage of glaucoma, regardless of whether the patient has never had ocular surgery or has undergone ten previous procedures. It can also be repeated as often as needed, making it easily titratable. A great candidate for MP3 treatment would be an older person who lives alone and has difficulty finding caregivers. This person would be greatly inconvenienced by the temporary vision loss following

a trabeculectomy or tube shunt, whereas they can go home following MP3 treatment and not worry about falling, risk of bleeding or infection. The procedure can be performed in the operating room or the office, and takes about as long as uncomplicated cataract surgery. Following MP3 treatment, patients are given topical steroids but there are no restrictions on the eye. As there is no incision, there is no risk of infection. In addition, it is very cost-effective compared with both medication and more invasive surgeries. With its excellent safety profile, it is possible that the MP3 device will have a prominent place in our arsenal against glaucoma. I await additional results on long-term trials examining the safety and efficacy of MicroPulse TSCPC.

Case study A recent case demonstrated the value that non-incisional, non-

glaucoma

(FIGURE 2) (Photo courtesy of IRIDEX)

pharmacologic therapies can have in improving the quality of life for glaucoma patients. A 91-year-old man presented on three different IOP-lowering medications. While otherwise doing well, he was struggling to care for himself, and his family and home health aides were having difficulties administering all of the drops every day. His visual acuity was 20/30 with a pressure of 21 mmHg in the right eye and 20/400 with a pressure of 40 mmHg in the left eye. On examination, he was found to have severe blepharitis, and his optic nerves demonstrated moderate damage in the right eye and advanced field loss in the left. When considering his treatment options, it was immediately obvious that he needed lower pressure in both eyes. An additional eyedrop would be optimal, but was not viable in his case. Additionally, given his already documented issues with drops, the severe

blepharitis and his age, incisional glaucoma surgery was deemed to be high risk with the prospect of little reward. Consequently, the patient was scheduled for MicroPulse laser trabeculoplasty with the 532 nm laser in the right eye, and MicroPulse cyclophotocoagulation with the 810 nm laser in the left eye. At one month post-procedure, his IOP was dramatically reduced, to 14 mmHg OD and 12 mmHg OS. The eye examination was otherwise unchanged. However, as his pressure was not at or below his target, in addition to the ongoing issues with eyedrop administration, medication was halted and he will be re-evaluated in one month’s time.

5. P.R. Egbert et al.,Arch. Ophthalmol. 2001; 119: 345-350. 6. A.M. Tan et al., Clin. Experimen.t Ophthalmol. 2010; 38: 266-272. 7. M.C. Aquino et al., Clin. Experimen.t Ophthalmol. 2014; 10: 1-7. 8. N. Radcliffe et al., Presented at the American Glaucoma Society annual meeting, 2015. 9. N. Ogata et al., Am. J. Ophthalmol. 2001; 132(3): 427-429. 10. C.J. Barnstable and J. Tombran-Tink. Prog. Ret. Eye Res. 2004; 23(5): 561-577. 11. A. Tan et al., Clin. Experiment. Ophthalmol. 2010; 38(3): 266-272.

REFERENCES 1. S.A. Pastor et al.,Ophthalmology 2001; 108: 2130-2138. 2. J.S. Aujla et al.,Clin. Experiment. Ophthalmol. 2013; 41(8): 761-772. 3. A.P. Rotchford et al.,Br. J. Ophthalmol. 2010; 94: 1180-1183. 4. S.J. Gedde et al., Am. J. Ophthalmol. 2012; 153: 789-803.

DR. NATHAN RADCLIFFE E: drradcliffe@gmail.com Dr Radcliffe directs the glaucoma service at New York University and operates at New York Eye Surgery Center. MARCH 2016 :: Ophthalmology Times Europe

focal points Curing DAVF type II progression DAVF (Intracranial dural arteriovenous fistula) is thought to be an acquired arteriovenous (AV) shunting disease, perhaps developing after venous sinus occlusion. DAVF is categorized as benign or aggressive depending on the pattern of venous drainage revealed by digital subtraction angiography. Dr A. Ibraheim, Dr. G. Mariatos

Introduction DAVF is connection between the meningeal arteries and veins. The following areas are the main site; lateral sinus, cavernous sinus, and sigmoid sinus. Some studies of intracranial vascular malformations showed 10-15% as DAVF. Their age presentation is between 40 to 60 years(7). It is accepted and agreed upon that DAVFs are acquired presenting later in life than AVMs (Arterio venous Malformations).(12) Brain tumor surgery, head injuries, or brain infection could be complicated with DAVF. Many neurologic symptoms may be associated with DAVF. These are secondary to ischemia and hemorrhage. These complications features may rate 3 - 11%.(10,16) Considerable number of cases present with ear symptoms (pulsatile tinnitus). Some studies showed 2 - 20% of DAVF cases with ear symptoms. (8, 9, 14) But the majority of DAVFs may remain a symptomatic. There are good reports of cases that have spontaneously resolved. Such findings suggesting higher incidence of DAVF than the reported studies.(11,13) The signs and symptoms are depending on the location of the fistula which is highly variable(19). Of the common non ophthalmic presentation of DAVFis pulsatile tinnitus and intracranial murmur. Of the ocular symptoms in cases with drainage by the ophthalmic veins are; conjunctival dilated vessels, exophthalmos, visual disturbance, and oculomotor paralysis.(17) Our case is completely asymptomatic and accidentally discovered on routine eye examination for glasses.

Case report DAVFs often present with the classic clinical findings of proptosis, chemosis, and bruit, but in our case it was asymptomatic and the only finding of investigation was disc swelling without any other signs and symptoms www.oteurope.com

This case starts in 1995, when a 51-year old man was referred to the eye clinic for bilateral optic disc swelling on a routine exam by an optician. On examination VA was 6/6 in both eyes with no ocular complain by the patient, not even headaches. Examination revealed bilateral disc oedema. The possibility of BIH was raised. He was fully investigated with MRI scan and also referred to neurology. FFA did show disc leakage. At that point the working diagnosis was idiopathic disc swelling. He was monitored in the eye clinic at various intervals. The patient was asymptomatic and his clinical image remained stable. Vision and fields also remained stable. In 2012, now at the age of 68 the patient was referred again now with symptoms of tightness in his head. Clinically there was no change in fundoscopy. The visual fields however revealed enlargement of the blind spot in both eyes. Again BIH needed to be excluded. Patient was referred once again for lumbar puncture and MRA. The opening pressure was now 32 in the LP. The MRA conclusion was of dural venous sinus occlusion on the right side. However a dural AV fistula needed to be excluded. A new MRA with catheter revealed a torcular dural AV fistula. Endovascular obliteration was performed. Patient was seen again after treatment. The tightness seems to have improved now. The Eye examination finding however is exactly the same. Visual fields are the same with slightly enlarged blind spot.

Conclusion The most feared complication of a cranial DAVF is brain hemorrhage. It is very important to recognize the typical findings of patients presenting with a DAVF then quickly proceeding with a cerebral angiogram to determine the exact location of the fistula and the appropriate treatment plan.

focal points By diagnosing and treating a DAVF as early as possible, the fatal complications can be averted. DAVFs often present with the classic clinical findings of proptosis, chemosis, and bruit. Treatment of a carotid cavernous DAVF is usually undertaken to protect against ocular and visual complications. Symptoms of DAVFs may be characterized further as either nonaggressive (e.g., tinnitus) or aggressive (e.g., intracerebral, subarachnoid, or subdural hemorrhage and neurologic deficits).(20-21) It may also present with an isolated but persistent or progressive headache, or symptoms and signs of a brain hemorrhage including sudden severe headache. Imaging by CT, CT angiography (CTA), MRI, and cerebral angiography play an important role in the investigation of patients with DAVFs. For a cranial DAVF, MRI is very helpful in defining the DAVF as CT may show only hemorrhage and not the fistula. The gold-standard for detection and characterization of a DAVF is a cerebral angiography on which a DAVF often appears as a complex vascular abnormality made up of abnormally large and tortuous dural arteries, and a large draining vein. Before any intervention, a non-enhanced CT must be done to rule out intracranial hemorrhage. Chronic venous congestion produces an area of low density on CT due to edema. Multidetector CTA, because of its rapid acquisition, can now provide high-resolution detail of vascular anatomy and has a temporal advantage over static CT.22 Earlier treatment of DAVFs that have these features is important to prevent complications. The risk of conversion from a benign to an aggressive DAVF is small but repeat angiography is indicated if the clinical picture appears to progress.(23)

REFRENCES 1. P. Lasjaunias, M. Chiu, K. TerBrugge, A. Tolia, M. Hurth and M. Bernstein, “Neurological Manifestations of Intrac- ranial Dural Arteriovenous Malformations,” Journal of Neurosurgery, Vol. 64, No. 5, 1986, pp. 724-730. doi:10.3171/jns.1986.64.5.0724 2. J. M. van Dijk, K. G. terBrugge, R. A. Willinsky and M. C. Wallace, “Clinical Course of Cranial Dural Arterio- venous Fistulas with Long-Term Persistent Cortical Ve- nous Reflux,” Stroke, Vol. 33, No. 5, 2002, pp. 1233- 1236. doi:10.1161/01.STR.0000014772.02908.44 3. J. A. Borden, J. K. Wu and W. A. Shucart, “A Proposed Classification for Spinal and Cranial Dural Arteriovenous Fistulous Malformations and Implications for Treatment,” Journal of Neurosurgery, Vol. 82, No. 2, 1995, pp. 166- 179. doi:10.3171/ jns.1995.82.2.0166 4. C. Cognard, Y. Gobin, L. Pierot, et al., “Cerebral Dural Arteriovenous Fistulas: Clinical and Angiographic Cor- relation with a Revised Classification of Venous Drain- age,” Radiology, Vol. 194, 1995, pp. 671-680. 5. J. A. Borden, J. K. Wu and W. A. Shucart, “A Proposed Classification for Spinal and Cranial Dural Arteriovenous Fistulous Malformations and Implications for Treatment,” Journal of Neurosurgery, Vol. 82, No. 2, 1995, pp. 166- 179. doi:10.3171/ jns.1995.82.2.0166 6. J. M. van Dijk, K. G. terBrugge, R. A. Willinsky and M. C. Wallace, “Clinical Course of Cranial Dural Arterio- venous Fistulas with Long-Term Persistent Cortical Ve- nous 7. Malek AM, Halbach VV, Higashida RT, Phatouros CC, Meyers PM, Dowd CF. Treatment of dural arteriovenous malformations and fistulas. Neurosurg Clin N Am. 2000;11:147–166. ix. 8. Waldvogel D, Mattle HP, Sturzenegger M, Schroth G. Pulsatile tinnitus--a review of 84 patients. J Neurol. 1998;245:137–142. 9. Sonmez G, Basekim CC, Ozturk E, Gungor A, Kizilkaya E. Imaging of pulsatile tinnitus: a review of 74 patients. Clin Imaging. 2007;31:102–108. 10. Lv X, Wu Z, Jiang C, Li Y, Yang X, Zhang Y, et al. Complication risk of endovascular embolization for cerebral arteriovenous malformation. Eur J Radiol. 2011;80:776–779. 11. Newton TH, Cronqvist S. Involvement of dural arteries in intracranial arteriovenous malformations. Radiology 1969;93:1071-8. 12. Borden JA, Wu JK, Shucart WA. A proposed classification for spinal and cranial dural arteriovenous fistulous malformations and implications for treatment. J Neurosurg 1995;82:166-179. 13. Sonmez G, Basekim CC, Ozturk E, Gungor A, Kizilkaya E. Imaging of pulsatile tinnitus: a review of 74 patients. Clin Imaging. 2007;31:102–108.

14. Waldvogel D, Mattle HP, Sturzenegger M, Schroth G. Pulsatile tinnitus--a review of 84 patients. J Neurol. 1998;245:137–142. 15. Herman JM, Spetzler RF, Bederson JB, Kurbat JM, Zabramski JM. Genesis of a dural arteriovenous malformation in a rat model. J Neurosurg. 1995;83:539–545. 16. Lv X, Wu Z, Jiang C, Li Y, Yang X, Zhang Y, et al. Complication risk of endovascular embolization for cerebral arteriovenous malformation. Eur J Radiol. 2011;80:776– 779. 17. Arai H, Melake M, Oishi H, et al. Transvenous embolization of dural carotid cavernous fistulas: a series of 44 consecutive patients. Am J Neuroradiol. 2010;31(4):651–55. 18. Gupta AK, Periakaruppan AL. Intracranial dural arteriovenous fistulas: a review. Indian J Radiol Imaging. 2009;19(1):43–48. 19. Bulters DO, Culliford D, Mathad N, et al. The natural history of cranial dural arteriovenous fistulae with cortical venous reflux – the significance of venous ectasia. Neurosurgery. 2012;70(2):312–18. 20. Lasjaunias P, Berenstein A. Surgical neuroangiography. Dural arteriovenous shunts. Vol 2.2. Germany: Springer-Verlag; 2004. p. 565-607. 21. T Cognard C, Gobin YP, Pierot L, Bailly AL, Houdart E, Casasco A, et al . Cerebral dural arteriovenous fistulas: Clinical and angiographic correlation with a revised classification of venous drainage. Radiology 1995;194:671-80. 22. Alatakis S, Koulouris G, Stuckey S. CT-Demonstrated transcalvarial channels diagnostic of dural arteriovenous fistula. AJNR Am J Neuroradiol 2005;26:2393-6. 23. Satomi J, van Dijk JM, Terbrugge K, Willinsky RA, Wallace MC. Benign cranial dural arteriovenous fistulas: Outcome of conservative management based on the natural history of the lesion. J Neurosurg 2002;97:767-70 24. Lasjaunias P, Berenstein A. Surgical neuroangiography. Dural arteriovenous shunts. Vol 2.2. Germany: Springer-Verlag; 2004. p. 565-607 25. Cognard C, Gobin YP, Pierot L, Bailly AL, Houdart E, Casasco A, et al . Cerebral dural arteriovenous fistulas: Clinical and angiographic

DR. G. MARIATOS, SPECIALTY DOCTOR Mr. A. Ibraheim MBChB, DORCS London, DO Dublin, FRCS Ed. FRCS RCPS Glas. FEBO (Europe), FRCOphth (UK), Board (IQ) A.IBRAHEIM / EYE CLINIC T: 07810311639 Barnsley Hospitals NHS Foundation Trust Gawber Rd. Barnsley S75 2EP MARCH 2016 :: Ophthalmology Times Europe

focal points Sale at Sotheby’s helps restore sight Gerhald Richter painting sells at auction to fund cataract surgery in Nepal Gerhard Richter painting donated to CBM by an anonymous donor has raised 44,500 Euros at a Sotheby’s auction. The artwork exhibits German painter Richter’s familiar layered and squeegee technique – a cool, colour photographic landscape with a spell of speedy, but splendid brush strokes spanning the surface and distorting the vision. The sale of the piece last month will go toward cataract surgeries in developing countries, the secret art admirer donating the artwork to the German charity Christoffel-Blindenmission (CBM) for a good cause. The proceeds will finance sightsaving surgeries for 1,483 people who were blind due to cataract.

IN SHORT A Gerhard Richter painting has raised 44,500 Euros at an auction held at Sotheby’s. The painting by the German artist was donated to CBM by an anonymous donor. The funds raised will go towards cataract surgeries for patients in Nepal.

Ophthalmologist Dr. Kermani: “Eyesight is so precious. It costs so little to give it back.” The inspiration behind the auction of Richter’s artwork is German ophthalmologist Dr. Omid Kermani. He and his colleagues from the eye-clinic Augenklinik am Neumarkt in Cologne already support the work of CBM. The ophthalmologists started a project called “eyes for eyes” to fund cataract surgeries in Nepal. For every cataract operation he and his colleagues perform they donate the money for an operation in Nepal. In the CBM - supported hospitals in Lahan and Biratnagar (Nepal), a staggering 97,000 people received cataract operations in 2014 and regained their sight. Named “Untitled (23 ‘Jan. 2015)” the artwork is an oil on colour photograph, sized 11.1 cm by 16.4 cm and was auctioned in the “Contemporary Art Day Auction” in London on the 11th of February. “This artwork helps us to save eyesight! A cataract surgery improves lives sustainably,” said CBM-Director Dr Rainer Brockhaus. “We thank the donor and the acquirer of the painting very much”. Sotheby’s also contributed to the good cause, by arranging all the logistics, including transportation, free of charge and waiving their commission, enabling all profits to go directly to the charity. Worldwide, there are approximately 20 million people who are blind due to cataract. It costs just 30 Euro to perform a cataract surgery at CBMprojects in developing countries. Ophthalmologist Dr. Kermani adds: “Eyesight is so precious. It costs so little to give it back.”

ERICA CROMPTON E: erica.crompton@ubm.com Erica is the Editor of Ophthalmology Times Europe and a freelance journalist. She has written about health for the Lancet, The Independent and the Mail on Sunday. An avid collector of 20h Century prints, she also studied at Chelsea College of Art.

The authors have no financial disclosures relating to the content of this article. www.oteurope.com

Image Credits: Sotheby’s

By Erica Crompton

product news FDA clearance for the OCULUS Pentacam AXL with Optical Biometry The new OCULUS Pentacam AXL has received the 510(k) clearance of the US Food and Drug Administration (FDA). The Pentacam AXL represents the systematic further development of the successful and time-proven Pentacam HR. Anterior segment tomography and optical biometry – all in one device and with a single measuring operation. Standard formulas, such as formulas for treated corneas, for toric IOLs, and raytracing formulas, are already integrated. The calculation of toric IOLs is based on the total corneal refractive power (TCRP), thus taking the influence of the posterior corneal surface into account. A comprehensive IOL database with IOL constants for the Pentacam AXL is also integrated. The Pentacam AXL offers a well-targeted screening process, Fast Screening Report, Belin/Ambrósio Enhanced Ectasia Display (early detection of corneal ectasia) and densitometric evaluation (Corneal Optical Densitometry & PNS) for every cataract patient. Whether aspherical, toric or multifocal: with the Cataract Pre-OP Display, the premium IOL can be selected in 4 steps. The IOL constants optimisation from Prof. Wolfgang Haigis permits a continuous enhancement of the results. Surgical data and post-refractive examination findings are secured with just a few clicks.

For further information on the new Pentacam AXL please contact your local OCULUS distributor or visit the website at www.pentacam.com. (Image Credits: OCULUS Optikgeräte GmbH)

New capsule fights against macular degeneration Macushield Gold, the AREDS2 formulation fortified with Meso-Zeaxanthin continues to fight against the progression of Macular Degeneration. It now brings together the previous combination treatment into a single, smaller “allin-one” capsule type, taken three times daily. It’s been developed by international experts in eye health to create an easier usage experience, whilst continuing to maintain healthy vision. This specific nutrient combination has been confirmed as the optimal nutrient combination for the maintenance of macular health in patients with Macular Degeneration by the AREDS2 study. As well as AREDS2, research published in peer-reviewed eye journals has shown that a supplement containing all three macular carotenoids, Lutein, Zeaxanthin and Meso-Zeaxanthin can uniquely enrich our protective macular pigment. This macular pigment is purely dietary in origin and acts as our body’s natural, protective filter for high energy blue light at the macula. For more information visit www.macushield.com. (Image Credits: MacuShield)

Saft’s Li-ion system expertise delivers miniaturized power pack for the IRIS bionic vision system Saft has worked with Pixium Vision to develop and manufacture stateof-the-art rechargeable lithium-ion (Li-ion) battery packs to power an innovative system that will help the fight against vision loss. The Saft battery packs provide Pixium Vision with a compact, lightweight high-performance portable power source for the innovative IRIS (Intelligent Retinal Implant System) bionic vision system that allows patients who have lost their sight to lead more independent lives. “The Li-ion battery system is critical to the success of IRIS, not only in providing reliable autonomous power, but also in helping to minimise the size and weight of the overall system to make it as easy and comfortable to use as possible. Our proven expertise in the design and volume manufacture of battery systems for high-tech medical applications was therefore a key factor in Pixium Vision’s decision to work with Saft,” said Ben Helminem, Director of Marketing and Strategic Development at Saft. (Image Credits: Saft)

MARCH 2016 :: Ophthalmology Times Europe

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product news Optical Express gains seal of approval from Plain English campaign Optical Express has been awarded the Crystal Mark – the official seal of approval of the Plain English campaign – for its eye surgery patient consent forms. The ‘terms and conditions’ contained in its surgery documents have also been certified by the internationally acclaimed mark. The mark now appears on over 21,000 documents in the UK and in other countries including the USA, Australia, South Africa and New Zealand. Among the leading health care organisations which have gained the Crystal Mark are NHS24 and the College of Optometrists. Optical Express is the biggest provider of laser eye surgery in the UK and Ireland. It is also a leading provider of lens replacement surgery. David Moulsdale, Chairman and Chief Executive of Optical Express, said: “It is an honour to be awarded the Crystal Mark, an internationally recognised accreditation for clear and simple communication. “We go to great lengths to educate our patients about the risks and benefits of laser eye surgery, which is the most frequently performed form of elective surgery worldwide and vastly improves the day-to-day lives of millions of people globally each year. Gaining the Crystal Mark shows that we are offering patients clear, concise information about eye surgery which does not hide anything with medical jargon or technical terms.” (Image Credits: Optical Express)

Oculoplastics module added to Volk’s eye check handheld ocular measurement device Volk Optical has added a new Oculoplastics Mode to its Volk Eye Check portable ophthalmic exam tool. With this mode, the handheld Volk Eye Check provides fast, objective and accurate pre- and post-op measurements for clinical and cosmetic lid surgeries. The Volk Eye Check is simple to operate with automatic report generation for documentation. The model analyses 26 datapoints in under one minute, providing precise binocular capture of measurements including: MRD1 and MRD2, plus two additional points on each lid; Palpebral Aperture and aperture at limbus; pupil diameter and iris diameter; and pupil eccentricity. In addition, a grid scale provides a convenient way to measure and compare landmarks such as brow position, and Margin Crease Distance. Objective documentation of these characteristics is useful for insurance reimbursement, as well as providing “Before and After” evidence for patients and clinicians. The Volk Eye Check’s touch-screen interface is easily navigated for use by a technician, nurse or doctor. Its real-time, accurate and objective results eliminate inter-clinician variability to enable quick decision making. The single-page Oculoplastics patient report includes side by side comparison diagram, and list of measurement values.

Also, the Oculoplastics Mode, the Volk Eye Check fully automates the analysis of ocular characteristics for general diagnosis in “Eye Check (EC)” Mode and for contact lens selection and fitting in “Contact Lens (CL)” Mode. The unit comes with a one-year warranty and ongoing software upgrade support. For more information visit www.volk.com. (Image Credits: Syno-Vital)

MARCH 2016 :: Ophthalmology Times Europe

Retina and Glaucoma Imaging Platform

The SPECTRALIS® system is an ophthalmic imaging platform with an upgradable, modular design. This platform allows clinicians to configure each SPECTRALIS to the specific diagnostic workflow in the practice or clinic. NS 95 (18%)

Options include: OCT, multiple laser fundus imaging modalities, wideﬁeld and ultra-wideﬁeld modules, scanning laser angiography and OCT angiography*.

www.SPECTRALIS.info

N 69 (12%)

TS 92 (2%)

T 51 (2%)

G 79 <1%

NI 95 (18%)

TI 129 (7%)

*Currently under development, not for sale yet.

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Product Name: TAPTIQOMÂŽ 15 micrograms/ml + 5 mg/ml eye drops, solution in single-dose container. Composition: One drop (about 30 Îźl) contains about 0.45 micrograms of taďŹ&#x201A;uprost and 0.15 mg of timolol. One single-dose container (0.3 ml) of eye drops contains 4.5 micrograms of taďŹ&#x201A;uprost and 1.5 mg of timolol. Please refer to the Summary of Product Characteristics (SmPC) for a full list of excipients. Indication: Reduction of intraocular pressure in adult patients with open angle glaucoma or ocular hypertension who are insufďŹ ciently responsive to topical monotherapy with beta-blockers or prostaglandin analogues and require a combination therapy, and who would beneďŹ t from preservative free eye drops. Posology and method of administration: Recommended dose is one drop in the conjunctival sac of the affected eye(s) once daily. Not to exceed one drop per day in the affected eye. Not recommended in children or adolescents (under the age of 18). In renal or hepatic impairment use with caution. To reduce systemic absorption, patients should be advised to use nasolacrimal occlusion or close the eyelids for 2 minutes after instillation. Excess solution should be wiped away to reduce the risk of darkening of eyelid skin. If more than one ophthalmic product is used, ďŹ ve minutes should separate their administration. Contact lenses should be removed before instillation. Contraindications: Hypersensitivity to the active substances or to any of the excipients. Reactive airway disease including bronchial asthma, or a history of bronchial asthma, severe chronic obstructive pulmonary disease. Sinus bradycardia, sick sinus syndrome, including sino-atrial block, second or third degree atrioventricular block not controlled with pace-maker. Overt cardiac failure, cardiogenic shock. Warnings and Precautions: Before initiating treatment, patients should be informed of the possibility of eyelash growth, darkening of the eyelid skin and increased iris pigmentation related to taďŹ&#x201A;uprost. These changes may be permanent, and lead to differences in appearance between the eyes if only one eye is treated. Similar cardiovascular, pulmonary and other adverse reactions as seen with systemic beta-adrenergic blocking agents may occur. The incidence of systemic adverse reactions after topical ophthalmic administration is lower than with systemic administration. Caution should be exercised when prescribing TAPTIQOM ÂŽ to patients with cardiac or severe peripheral vascular disorders eg Raynaudâ&#x20AC;&#x2122;s disease or syndrome. Use with caution in patients with mild/moderate COPD and in patients subject to spontaneous hypoglycaemia or labile diabetes. Beta-blockers may mask signs of hyperthyroidism and block systemic beta-agonist effects such as those of adrenaline. Anaesthetists should be informed when a patient is receiving timolol. Patients with a history of severe anaphylactic reaction may be more reactive to repeated challenge with such allergens and be unresponsive to the usual doses of adrenaline used to treat anaphylactic reactions. The known effects of systemic beta blockers may be potentiated when TAPTIQOMÂŽ is given concomitantly. The use of two topical beta-blockers is not recommended. Patients with corneal disease should be treated with caution as ophthalmic beta-blockers may induce dry eyes. When timolol is used to reduce elevated intraocular pressure in angle-closure glaucoma, always use a miotic. Caution is recommended when using taďŹ&#x201A;uprost in aphakic patients, pseudophakic patients with torn posterior lens capsule or anterior chamber lenses, and in patients with known risk factors for cystoid macular oedema or iritis/uveitis. Please see the SmPC for further information. Interactions with other medicinal products: Potential for hypotension / marked bradycardia when administered with oral calcium channel blockers, beta-adrenergic blockers, anti-arrhythmics, digitalis glycosides, parasympathomimetics and guanethedine. Please refer to the SmPC. Pregnancy: Do not use in women of childbearing age/potential unless adequate contraceptive measures are in place. Breast-feeding: It is not recommended to breast-feed if treatment with TAPTIQOMÂŽ is required. Driving and using machines: If transient blurred vision occurs on instillation, the patient should not drive or use machines until clear vision returns. Undesirable Effects: Conjunctival/ocular hyperaemia occurred in approximately 7% of patients participating in clinical studies with TAPTIQOMÂŽ. Other common side effects include: eye pruritus, eye pain, change of eyelashes (increased length, thickness and number of lashes), eyelash discolouration, eye irritation, foreign body sensation, blurred vision, photophobia. Adverse reactions that have been seen with either of the active substances (taďŹ&#x201A;uprost or timolol) and may potentially occur also with TAPTIQOMÂŽ include: increased iris pigmentation, anterior chamber cells/ďŹ&#x201A;are, iritis/uveitis, deepening of eyelid sulcus, hypertrichosis of eyelid, exacerbation of asthma, dyspnea, allergy, angioedema, urticaria, anaphylaxis, hypoglycaemia, syncope, ptosis, bradycardia, chest pain, palpitations, oedema, cardiac arrest, heart block, AV block, cardiac failure. Please also see the SmPC. Overdose: Treatment should be symptomatic and supportive. Special Precautions for Storage: Store in a refrigerator (2Â°C - 8Â°C). After opening the foil pouch keep the single-dose containers in the original pouch and do not store above 25Â°C. Discard open single-dose containers with any remaining solution immediately after use. Package quantities and basic NHS cost: 30 x 0.3ml single-dose containers ÂŁ14.50. Product Licence Holder: Santen Oy, Niittyhaankatu 20, 33720 Tampere, Finland (PL 16058/0012) Price: 30 x 0.3ml single-dose containers ÂŁ14.50. Date of Authorisation: 30/10/2014 POM Date of Prescribing Information: 31/05/2015

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Santen UK Limited (Email medinfo@santen.co.uk or telephone: 0845 075 4863). TAPTIQOM is a registered trademark of Santen Pharmaceuticals Co., Ltd.

References: 1.HollĂł G et al. Fixed-Dose Combination of TaďŹ&#x201A;uprost and Timolol in the Treatment of Open-Angle Glaucoma and Ocular Hypertension: Comparison with Other Fixed-Combination Products. Adv Ther. 2014; 31: 932-944 2.Taptiqom SPC, available at http://www.mhra.gov.uk/home/groups/ spcpil/documents/spcpil/con1418969000862.pdf, accessed 11.08.15 Job code: STN 0817 TAP 00018b (EU) Date of preparation: January 2016