Oraya Supplement

Supplement Dec 2014/Jan 2015

See the Impact of Oraya Therapy on Wet AMD Patients Saturday 13 September 2014 14th EURETINA Congress London, UK

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Introduction Oraya Therapy: Reducing the Burden of Anti-VEGF Injections

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he advent of anti-VEGF therapies for neovascular agerelated macular degeneration in the mid-2000s were nothing short of revolutionary. Where earlier treatments at best slowed vision loss in an inevitable march toward blindness, many wet AMD patients now actually saw vision improve.

However, anti-VEGF treatment comes with a cost: frequent intraocular injections for years if not the rest of patients’ lives.

These injections can be painful, they expose patients to side effects ranging from vitreous floaters and inflammation to a small but real risk of major ocular complications including geographic atrophy, retinal detachment, traumatic cataract and endophthalmitis. Risks are also slightly increased for certain systemic side effects including heart attack, stroke or other thromboembolic events. Growing numbers of patients on extended anti-VEGF therapy also strain the resources of ophthalmic offices, while the costs threaten national health service budgets.

RADIATION THERAPY Any treatment that might reduce the number of injections needed would help. Taking a cue from oncology, where radiation therapy often complements anti-VEGF therapy, Oraya Therapeutics developed the IRay® stereotactic radiotherapy system for treating wet AMD. Oraya uses a low-energy (100kVp) X-ray source similar to that found in dental radiography. The X-ray is collimated into a narrow beam that enables rapid dose fall-off, precise targeting limited to the macula, and minimal radiation scatter that is easily shielded. During treatment, the proprietary I-Guide™ Eye Stabilization Device, a vacuum-coupled contact lens with integrated optical reflectors, gently stabilizes the globe, while the imaging system tracks the eye to ensure accurate beam delivery. Oraya’s stereotactic radiotherapy system employs sub-

The IRay® Radiotherapy System

See the Impact of Oraya Therapy on Wet AMD Patients

This map shows the countries and locations where the Oraya Therapy is available

millimeter precision in beam placement with real time monitoring of energy delivery.

In INTREPID, a one-year clinical trial involving 230 wet AMD patients already receiving anti-VEGF injections, a single 20-minute treatment with the IRay® device reduced the number of injections required by 32 percent compared with sham treatment controls (p=0.0014, Jackson T et al. Ophthalmology.

Sept 2013. 120(9) 1893–1900).

At two years, Oraya Therapy treated-patients required 26 percent fewer injections (p=0.009, Jackson T et al.

Ophthalmology. In press. Published Online: September 07, 2014). A subgroup of ideal responders, identified at the one year endpoint as patients with lesions characterized by both a diameter of 4mm or less and abnormally large macular volume (essentially actively leaking), required 45 percent fewer injections at two years (p=0.0002) while maintaining vision (VA superiority of 4.43, p=0.24).

These favourable results have spurred rapid expansion of Oraya Therapy in Europe. It is now commercially available in the UK, Germany and Switzerland, with a rapidly growing portion of the patient population covered by insurance reimbursement. We present ongoing research documenting the safety and efficacy of this novel approach to reduce the burden associated with treating neovascular AMD.

Three-year Safety

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Stereotactic radiotherapy induces localised microvascular changes, but for most patients they are not visually significant Tim Jackson PhD, FRCOphth t.jackson1@nhs.net

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adiotherapy is known to present long-term risks, including radiation retinopathy and microvasculopathy. For this reason, patients participating in INTREPID, a clinical trial of stereotactic radiotherapy for neovascular AMD, were followed after the study’s one-year primary endpoint, receiving safety assessments at two years and three years after a single radiation treatment.

Over the three years, about 30 percent of participants in the study’s radiation treatment arms developed small localized microvascular abnormalities (MVAs), said Tim Jackson PhD, FRCOphth, consultant ophthalmic surgeon at King’s College London, UK. However, the presence of radiotherapy-induced MVAs did not significantly modify visual outcomes in the majority of those with MVAs. Several radiationinduced MVAs also regressed, suggesting they may resolve in time.

TOUGH CASES The double-blind prospective study included 230 patients who had neovascular AMD for up to three years, and had at least three anti-VEGF treatments in the previous 12 months. “These tend to be the heavier anti-VEGF users,” Dr Jackson said. Lesion size was limited to 6.0mm, “though in hindsight, maybe we could have limited the lesion to 4.0mm because the 90 percent isodose [the area that receives at least 90 percent of the prescribed dose] only extends up to 4.0mm.” All received an initial dose of ranibizumab and were randomised 2:1 to receive 16Gy radiation or sham radiation treatment, or 2:1 to receive 24Gy radiation or sham treatment.

“... of the 18 cases we had... from year two... half of those showed full or partial resolution...”

The radiation received amounted to about 10 percent of a head CT scan. “It’s about the proportion of a dental X-ray,” Dr Jackson said. Delivered from three beams sequentially, radiation converges on a 4.0mm target surrounded by a minimally irradiated penumbra that extends to 6mm. Patients were evaluated monthly for 12 months, receiving additional anti-VEGF injections as required.

The study hit its primary endpoint at 12 months by reducing injections by about a third, with comparable visual acuity results between treatment and control arms. Patients then returned to usual treatment. At two years, safety and efficacy data were collected. Injections were reduced 26 percent in the treated groups compared with controls (P=0.009), and vision changes were similar between treated and control subjects. At 36 months only safety data were collected.

Safety was assessed through colour fundus imaging and fluorescein angiography. Images were reviewed by a grading

panel looking specifically for evidence of microvascular change. Suspects were forwarded to senior graders to determine if lesions might be radiationrelated. Suspect cases were sent to an independent masked review by experts for final confirmation.

Radiotherapy-induced MVAs were distinguishable by reading center analysis from abnormalities associated with wet AMD progression, Dr Jackson said. In colour pairs, cotton wool spots and retinal haemorrhage in the nerve fibre layer could be seen in areas not occupied by neovascular AMD lesions. In angiograms, capillary non-perfusion marked by decreased fluorescence in a perivascular distribution was a particularly strong indicator of radiation involvement, Dr Jackson said. Other signs were intra-retinal telangiectasia marked by dilated or tortuous retina arterioles or capillaries in areas outside nvAMD lesions, and vascular sheathing with a glistening or white perivascular appearance indicating presence of gliosis or fibrosis. Intraretinal oedema, marked by hyporeflective areas within the neurosensory retina but outside nvAMD lesions, was also evident on OCT.

SAFETY RESULTS Overall, at month 36, 33 of 122 radiation-treated patients showed MVA attributable to radiotherapy that had not regressed, Dr Jackson said. “Interestingly, of the 18 cases we had moving forward from year two to year three, half of those showed full or partial resolution, so these lesions seemed to pop up and then a fair proportion seemed to resolve. This is very different from the normal radiation retinopathy.”

Most radiotherapy-induced microangiopathies were located in the inferior-nasal macula and their average size was 4.1mm2, or less than two disc areas. Most lesions fell within the 6.0mm treatment penumbra area, with nearly half occurring outside of the 4mm diameter area that received the full prescribed dose. There was no correlation between MVA location and treatment targeting.

Five lesions were located near the fovea, potentially affecting vision loss, Dr Jackson said. “Though in fairness, most of the vision loss was affected by the disease itself.” At 36 months, there was no significant difference in visual outcomes across the treatment subsets, including radiotherapy patients with MVA, radiotherapy patients without MVA and patients treated with anti-VEGF only.

Most radiotherapy induce MVAs were also mild. None were picked up in the first year, 18 in the second, and 37 in the third.

95 percent of the lesions were picked up by the reading centres only and not noticed by the clinicians treating the patients.

“They are extremely subtle unless you know to look for them.”

While MVAs do appear to be radiation related, the presence of similar lesions have been reported in about 14 percent of treatment naïve wet AMD eyes and eight percent of dry AMD eyes (Jackson et al, Retina 34(3): 568-75, 2014), indicating the complexity of this type of image evaluation, he added. “It can be a feature of AMD; it’s possible some of these may be AMD itself. But I think there is genuinely something going on.”

“If you look closely enough you can find MVAs in a fair proportion of patients. But they don’t appear to affect vision and they may evolve; they may get better,” Dr Jackson concluded.

See the Impact of Oraya Therapy on Wet AMD Patients

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Is Retinal Radiotherapy Safe?

Ian Rennie MB, ChB, FRCS, FRCOphth i.g.rennie@sheffield.ac.uk

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s treatment side effects go, radiation retinopathy has a bad reputation. It is often perceived as inevitable, permanent, always associated with visual loss and untreatable.

The reality, however, is quite different, said Ian Rennie MB, ChB, FRCS, FRCOphth, an ocular oncologist at Royal Hallamshire Hospital, Sheffield, UK. Prof Rennie has extensive research and clinical experience with a wide range of ocular radiation treatments. These include stereotactic radiosurgery, proton beam radiotherapy and radioactive plaque.

In fact, clinically significant radiation retinopathy is rare below a total dose of 30Gy, and many patients receiving higher doses do not develop retinopathy, Prof Rennie said. Cases that do occur generally develop within 36 months of treatment and many are transient, with vision often minimally impaired or completely unaffected. Moreover, radiation retinopathy is treatable with anti-VEGF agents.

“... six or seven years ago, I would have said radiation retinopathy is untreatable generally, but not now” studies have found endothelial cell loss and capillary closure at doses of 15-20Gy, and human retinal damage has been reported sporadically after 11-20Gy exposure. But those reports are the exception rather than the rule, and often involve confounding factors, such as chemotherapy, which can increase sensitivity to radiation, he said.

In general, the literature shows that a minimum dose of 30-35Gy cephalic radiation is necessary before significant retinal effects are seen, Prof Rennie said. At 60Gy, half of patients will experience retinal changes, rising to 75– 85 percent at 70-80Gy. Many ocular oncology treatments greatly exceed the 16Gy dose recommended for Oraya Therapy, Prof Rennie pointed out.

For example, treating uveal melanoma can involve stereotactic radiosurgery delivering 35-70Gy gamma radiation, proton beam radiotherapy delivering the gamma equivalent of 58Gy, or ruthenium 106 plaque delivering a beta particle dose of 350-800Gy. How radiation is delivered also matters, Prof Rennie said. In general, fractionating the total dose into multiple smaller doses reduces retinopathy risk.

TIME OF ONSET Oraya Therapy delivers 16Gy, which is below the 30Gy significance threshold

Based on these and other general characteristics of retinal radiotherapy, the risk of radiation retinopathy from Oraya Therapy stereotactic radiotherapy for neovascular AMD should be quite limited. Indeed, in examining patients from the INTREPID Phase II clinical trial of Oraya Therapy, Dr Rennie found the retinal changes that may be due to radiation mostly slight and not clinically significant.

Overall, about one-third of INTREPID patients in the radiation treatment arms, which received either 16Gy or 24Gy doses, had suspected radiation-induced microvascular abnormalities, but the majority were mild and difficult to visualise, he added.

MINIMUM THRESHOLD Microvascular abnormalities are the indication of radiation retinopathy most often seen in Oraya Therapy patients, but other clinical features are common in oncology, Prof Rennie said. These include microaneurysms, telangiectasia, intraretinal haemorrhages, capillary non-perfusion, exudates and cottonwool spots. “Many of these are the same as you see in diabetic retinopathy.”

Whether there is a minimum threshold dose for radiation retinopathy is a complex question, Prof Rennie noted. Animal

See the Impact of Oraya Therapy on Wet AMD Patients

Overall, onset of retinopathy due to radioactive plaque occurs at a mean of 14.2 months after treatment, ranging from four to 32 months. External beam radiation may take longer, with a mean 18.7 months ranging from seven to 36 months (Brown et al. Ophthalmology 1982). These timeframes are consistent with onset of MVAs in the INTREPID study, which mostly appeared in the second and third year of follow up, Prof Rennie noted. “After three years the likelihood of developing radiation retinopathy declines dramatically.”

Contrary to conventional wisdom regarding the permanence of radiation retinopathy, many patients in the trial also saw MVAs regress or completely resolve, again consistent with Prof Rennie’s clinical experience with oncology patients. Visual loss is not inevitable result of radiation retinopathy. Prof Rennie illustrated this point by showing fundal images of patient with part of the retina close to the optic disc completely destroyed by plaque treatment who still retained normal vision in the eye.

Finally, as with other retinopathies, the radiation variety is now treatable with anti-VEGF therapy. Prof Rennie showed a case of extensive retinopathy following 58Gy proton beam exposure that resolved completely with three injections of bevacizumab. “If I had given this lecture six or seven years ago, I would have said radiation retinopathy is untreatable generally, but not now,” he said.

Patient Experience

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Dissatisfaction with injections drives interest in radiation therapy, most patients satisfied Tariq Aslam DM (Oxon), FRCSEd (Ophth), MBChB, MA (Oxon), Dip IT, PhD tariq.aslam@manchester.ac.uk

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urveys of patients treated with Oraya Therapy stereotactic radiotherapy for neovascular AMD at Manchester Royal Eye Hospital, UK, found most tolerated the 20-minute procedure well and would recommend it to friends or family members. Desire to reduce anti-VEGF injections most often drove the treatment decision, said Tariq Aslam DM (Oxon), FRCSEd (Ophth), MBChB, MA( Oxon), Dip IT, PhD. A minority of patients treated in the programme’s first year saw dramatic reductions in anti-VEGF injections needed after radiotherapy, Prof Aslam said. However, he was not able to identify clinical indicators predicting a better response.

“The outcomes were sometimes very, very, good, (but) we found we weren’t able to necessarily predict those from the nature of the condition beforehand.” Pooling data from other studies might help better identify patients who might benefit more from the treatment, he added.

PRECONCEPTIONS While bad experiences with anti-VEGF injections might be expected to motivate patients to seek alternate AMD treatments, the first five patients Prof Aslam treated all reported tolerating injections when surveyed by an independent investigator.

Responses to an open-ended question on their injection experience included “not too bad” and “a necessary evil”. Nonetheless, reducing the number of injections was the top response when asked why they decided to take Oraya Therapy, and what results they hoped to achieve.

However, Prof Aslam also reported having patients refuse anti-VEGF treatment, or expect a cure with one injection based on incorrect preconceptions. He emphasized considering the individual experience of patients, and carefully explaining what they can realistically expect from therapies to guide treatment decisions.

Asked about their experience after radiotherapy, patients on average rated their level of understanding of the procedure, comfort following the procedure and willingness to recommend the treatment at nine-plus on a scale of one to 10. The duration, comfort and experience of the radiation procedure itself scored lower, in the six to eight range.

Drilling down, Prof Aslam found one patient who wished she had been advised to remove her dentures before the procedure, and a few cases where targeting three separate beams was difficult. “These are treatments we gave very early on in development of the machine and software, and those problems have been addressed in the new software,” he noted.

CLINICAL OUTCOMES Looking at clinical outcomes for his first 10 patients, Prof Aslam found four cases of very strong responses. One patient went from needing four injections in the six months before Oraya Therapy to none in the six months after; two went from five before to one after; and one from nine to two. Visual acuity also improved or was stable in these patients. “It wasn’t a drop of a quarter or a third or even half, but a much more dramatic response for these patients.”

On the other hand, five cases responded less dramatically, with injections falling from four before radiotherapy to three after in three cases, and actually increasing from three before to four after in one case. Another patient went from visual acuity of 0.86 logMAR, or about 20/140, before to 1.1 logMAR, or 20/250, after.

Looking at lesion size, choroidal neovascularization type, OCT findings and central retinal thickness before and after radiotherapy, Prof Aslam found no pattern predicting better outcomes. He followed treatment guidelines derived from analysis of the INTREPID Phase II clinical trial, suggesting patients with lesions of 4.0mm or less and actively leaking lesions with minimal fibrosis are better responders. However, one of his strongest responders had fibrosis. He initially resisted treating her, but did so because she was keen for it, suggesting there is value in keeping an open mind and considering patient desires in case selection.

Overall, the study demonstrated the importance of advising patients on what to expect, and not expect, from radiotherapy, Prof Aslam concluded. While comfort levels were good, he expects them to improve with refinements to the device hardware and software.

Most important, Prof Aslam hopes that sharing data on more patients will help identify patients who should have Oraya Therapy as well as perhaps those who should not. “Maybe as we get more information in future it might allow more of our patients to be in (the strong responder) group for their own benefit.”

One-year Outcomes Retinal thickness, frequency of anti-VEGF injections reduced six months after radiotherapy Katja Hatz MD khatz@vistaklinik.ch

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atients with chronic need for anti-VEGF therapy to counter persistent exudation generally experienced significantly reduced retinal thickness and stable visual acuity between three and six months after treatment with Oraya Therapy stereotactic radiotherapy for neovascular AMD, this following an initial rise in central retinal thickness with

a corresponding slight decrease in visual acuity immediately following treatment in a part of the cases, said Katja Hatz MD, of Vista Klinik, Binningen, Switzerland. Subsequently most patients saw subretinal oedema resolve completely with reduced frequency of anti-VEGF, and visual acuity remain at least stable compared to baseline.

See the Impact of Oraya Therapy on Wet AMD Patients

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Based on about 50 patients treated in her programme’s first year, Dr Hatz sees the reduction in anti-VEGF treatment and the consequent reduction in treatment burden as Oraya Therapy’s main benefit. It may also reduce persistent choroidal neovascular activity in poor responders, she added.

CAUTIOUS START Dr Hatz took extra caution selecting her first Oraya Therapy patients.

Best corrected visual acuity in the first six patients averaged about 0.42 decimal, or about 20/45. At one month post treatment, that dipped to about 0.35 decimal, or about 20/55, with a corresponding mean increase in CRT of about 35 microns. From there, CRT plunged quickly, to about 165 microns below baseline at six months, and 170 microns below at nine months. Visual acuity also recovered to baseline or better.

Broadening patient selection criteria, Dr Hatz saw the same pattern repeated among 12 patients who already finished the six months follow-up with a mean 0.42 decimal baseline visual but less retinal swelling, with VA rising above baseline. 22 patients who had been followed by at least three months with mean baseline VA of 0.46 recovered even quicker, returning to baseline at three months. “Central retinal thickness seems to be significantly reduced between three and six months. That’s what we tell our patients now,” Dr Hatz said.

DIFFERENT LESION TYPES Overall, Dr Hatz and colleagues adhered to treatment guidelines suggesting lesions of no more than 4.0mm diameter. However, many types of lesions were treated to good effect, she said.

The first patient treated was diagnosed in 2011 with BCVA of 0.4, and treated once with low-fluence photodynamic therapy and 21 times with anti-VEGF at four to five week intervals.

Subretinal fluid remained after all treatments, and at baseline he suffered from severe sicca symptoms, Dr Hatz said. One month after radiotherapy, VA dropped to 0.3, or about 20/60, with subretinal fluid increasing. At two months, VA improved and subretinal swelling declined. Between six and nine months, subretinal fluid disappeared entirely, and anti-VEGF interval was extended to six weeks. At one year, BCVA improved to 0.5, or 20/40, at eight weeks anti-VEGF intervals, later lengthened to 10 weeks. “For this patient it is a very nice result. For the first time we were able to extend the intervals.”

A second patient with a smaller lesion controlled with anti-VEGF every four weeks was treated with the goal of reducing frequency,

Dr Hatz said. “She already had 35 injections and was tired.” At three months, the interval was increased to six weeks, at six months to eight to 10 weeks, and at nine months to 12 weeks, with BCVA returning to the baseline of 0.63, or about 20/32 at six months and steady thereafter.

Another patient with a small lesion not completely controlled after 16 anti-VEGF injections at four-week intervals, showed trace cystoid macular oedema after treatment. At three months after radiotherapy, the retina was completely dry. At four months the injection interval was extended to six weeks and is now eight weeks, Dr Hatz said.

A patient with a larger lesion, but still within 4.0mm diameter, had been treated 35 times at four week intervals. Two months after radiotherapy her subretinal fluid disappeared. At six months she went to an eight week injection interval, Dr Hatz said.

A progressed lesion with BCVA of 0.1, or 20/200, subretinal fibrosis and a small areal of pigment epithelium atrophy received radiotherapy with the goal of slowing growth of a scotoma, Dr Hatz said. “We didn’t want to treat with Oraya at first,” Dr Hatz said. But the patient was worried and the lesion was within the 4.0mm spot, so treatment went forward. At three months the lesion was dry, at six months treatment extended to eight-week intervals, and at nine months to 12-week intervals without further vision loss.

“These are very different cases we have been treating in Switzerland.

In all of our patients treatment was well tolerated; so far we don’t have safety concerns, but follow-up times are short,” Dr Hatz said.

Patient Selection for Best Wet AMD Outcomes Lesions under 4.0mm with active leakage respond best to radiation therapy Salvatore Grisanti MD salvatore.grisanti@uk-sh.de

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hile injected medications typically address neovascularization wherever it occurs in the eye, radiation is effective only in tissues directly exposed to a therapeutic dose, said Salvatore Grisanti MD, Head of the University Eye Clinic of Lübeck, Germany. As a result, patients with leaking retinal lesions that can be completely covered by the 4.0mm radiation beam spot are most likely to respond well to Oraya Therapy stereotactic radiotherapy for neovascular AMD. Much like photodynamic therapy, radiation is mechanistic See the Impact of Oraya Therapy on Wet AMD Patients

in its approach, working only within precisely targeted areas, Prof Grisanti explained. Among the most accurate devices for delivering radiation to the eye, the Oraya IRay® system delivers a 90 percent isodose over a 4.0mm diameter area, with the dose falling off very quickly outside this zone. As a result, any part of a lesion extending beyond the 4.0mm zone will not receive a therapeutic dose and will likely remain active.

While radiation is anti-angiogenic, anti-proliferative and anti-inflammatory, it does not reverse scar tissue. Therefore,

eyes with lesions that are still undergoing active proliferation, which produces fluid leakage that also increase lesion volume, are more likely to respond than lesions that have advanced to fibrosis, which have central scars that are not affected by radiation, Prof Grisanti added. Also, fibrous lesions grow centrifugally, often remaining proliferative at their edges. This potentially places more of the active lesion beyond the edge of the effective dose area.

These theoretical predictions are borne out by the results of the INTREPID Phase II clinical trial combining one IRay® treatment with ongoing anti-VEGF injections as needed, Prof Grisanti said. Subgroup analysis revealed that lesions that were both smaller in diameter than 4.0mm and had macular volume greater than 7.4mm3 required fewer injections (P=0.0010) and saw greater fluid reduction (P=0.0101) than lesions with any combination of a larger diameter or smaller volume. Patients without fibrosis also required fewer injections than those with fibrosis (P=0.0044).

TARGET PATIENTS Colour fundus photography, fluorescein angiography and OCT are useful for identifying suitable patients, Prof Grisanti said.

“You can measure very well to see if the lesion will be inside the treatment area.”

More than half of wet AMD patients have lesions less than 4.0mm in diameter within one year of diagnosis, Prof Grisanti

said. The CATT trial comparing ranibizumab and bevacizumab put the figure at 61–65 percent (NEJM April 2011), while a prospective audit of exudative AMD cases in treatment naïve eyes put the number at 88– 94 percent (Giles MC et al.

IOVS July 2013). These are all potential high responders, and treatment should be considered before the lesion grows too large for Oraya Therapy, he added.

Some patients may be categorized as “fast metabolizer”. These patients that respond to anti-VEGF injections but require frequent injections to keep retinal fluid down are good candidates for Oraya Therapy, Prof Grisanti said. Often, fewer injections are required to maintain these patients after radiotherapy.

Patients who do not achieve complete elimination of subretinal fluid with monthly injections, but see fluid increase with less frequent injections may also respond to Oraya Therapy.

“But it’s very important to look at the size of the lesion,” Prof Grisanti advised.

Reducing injection frequency not only improves patients’ lives.

It may also improve outcomes, Prof Grisanti noted. Over time, patients tend to drift away from frequent injection regimens, resulting in vision loss after a year or so of treatment.

Treating Naïve Patients Christopher Brand FRCOphth Christopher.Brand@sth.nhs.uk

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hile Oraya Therapy clinical trials to date have included patients already receiving anti-VEGF injections for exudative age-related macular degeneration, the best chance for success may be with treatment-naïve patients in the induction phase, said Christopher Brand FRCOphth, Consulting Ophthalmologist, Sheffield Teaching Hospitals, UK. Much as early anti-VEGF treatment prevents vision loss, combining radiotherapy with initial anti-VEGF therapy may increase its clinical effectiveness.

Three months into this new service delivery in which qualifying newly diagnosed wet AMD patients receive Oraya Therapy two

“When do we find these characteristics? We find them in the new wet AMD patient” days after their first anti-VEGF injection, followed by two more injections at four or five week intervals, Dr Brand has yet to see a patient requiring more than the initially prescribed three injections.

However, as of mid-September, only a handful of patients had reached their first follow-up.

“The numbers are small and these are early days,” Dr Brand acknowledged. The “honeymoon” phase that often accompanies

initial anti-VEGF treatment may be influencing the results. He believes the argument for treating naïve wet AMD patients with radiotherapy will become compelling.

PREVENTING DAMAGE Dr Brand pointed out that the INTREPID trial and subsequent clinical experience make very clear who best responds to Oraya Therapy – patients with active choroidal neovascular membrane with small lesion size, significant fluid, which is another marker of an active lesion, as well as minimal or no fibrosis. “When do we find these characteristics? We find them in the new wet AMD patient,” he said.

Dr Brand suggested that applying the lessons of the INTREPID trial to less advanced patients makes perfect clinical sense. He drew an analogy to the ANCHOR and MARINA anti-VEGF trials, which established the efficacy of ranibizumab for treating wet AMD patients with active lesions and visual acuity from 6/12 to 6/96. “I know of no ophthalmologist in the UK who would not consider treating a patient with symptomatic wet AMD with a visual acuity of 6/9. The trial evidence didn’t directly support that at the time, but common sense says ‘let’s treat that patient’.” Subsequent studies confirmed that clinical insight, showing that early anti-VEGF treatment can prevent vision loss and gives better visual outcomes at 12 and 24 months, he added.

Dr Brand is hopeful the case for early Oraya Therapy will be similarly vindicated, and urged colleagues to recommend it to patients with suitable lesions; his NHS Trust has set up a protocol to do just that.

See the Impact of Oraya Therapy on Wet AMD Patients

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Sponsored by an educational grant from Oraya Therapeutics, Inc.

In the USA, the IRay速 Radiotherapy System is an investigational device and is not available for sale.

Further information about Oraya Therapy and Oraya Therapeutics, Inc. can be found at www.orayainc.com

Supplement Dec 2014/Jan 2015