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Fundus Photos Look Good on an iPhone

Nonmydriatic fundus photos displayed on an Apple iPhone 3G have sufficient quality to enable consulting ophthalmologists to help emergency physicians diagnose acute, sight-threatening conditions such as papilledema and malignant  hypertension, according to a report by an interdisciplinary team of Atlanta researchers.

Indeed, a pair of trained reviewers tended to rate the quality of photos viewed on an iPhone higher than those viewed on a 19-inch LCD desktop screen, the group said in a letter to Archives of Ophthalmology.1

Study history. This was the group’s fourth publication to emerge since 2011 from FOTO-ED, a project that is investigating the use of nonmydriatic fundus photos to assess patients whose symptoms suggest a possible neuro-ophthalmic emergency. The lead investigators have clinical specialties in neuro-ophthalmology, neurology, neurologic surgery, and emergency medicine.

The researchers began considering the merits of photo-based diagnosis because emergency physicians often find direct ophthalmoscopy too difficult to perform, said Beau B. Bruce, MD, MS, assistant professor of ophthalmology and neurology, and medical director of ophthalmic clinical trials at Emory University.

“We had all seen young women who came into the ER with a headache and papilledema, but nobody had examined their eyes,” Dr. Bruce said. “So the emergency physicians missed the fact that these patients had increased intracranial pressure, and the patients had a devastating visual loss because of it.”

The FOTO-ED scientists reported last spring that, with brief training, nurse practitioners could take high-quality nonmydriatic fundus photos in at least one eye of 85 percent of the study subjects.2  

Current report. The latest results were from a pilot study aimed at learning whether smartphones might extend and amplify the day-to-day clinical impact of what the researchers had learned so far.

“We asked: How can we facilitate this for the ophthalmologist who is going to be reviewing these photos remotely, when the emergency department doctors aren’t sure what the photos show?” Dr. Bruce said.

“This is a great tool to help ophthalmologists triage patients remotely. It will help them do their jobs in a wider variety of places—such as when they’re covering several emergency departments at the same time,” he said. “Or maybe looking at ER photos on a smartphone could help them determine how quickly they need to see the patient.”

The researchers noted in their report, “Our results support the iPhone’s display as a potential component in a telemedicine network. We are not suggesting using the iPhone to screen for subtle conditions (e.g., diabetic retinopathy) or as a replacement for in-person ophthalmologic consultation. Rather, we believe the iPhone, and similar devices, in combination with nonmydriatic photography can complement ophthalmologic consultations in settings such as the emergency department by allowing for rapid and remote identification of obvious conditions affecting the posterior pole.”

—Linda Roach 

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1 Lamirel C et al. Arch Ophthalmol. 2012;130(7):939-940.

2 Lamirel C et al. Ophthalmology. 2012;119(3):617-624.

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Dr. Bruce reports no related financial interests.    

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More in Chicago
Smartphones (Mobile Technology): An Update. Learn to put the power of smartphones and tablets to work for you. Apps and industry trends will be discussed. When: Sunday, Nov. 11, noon-1:30 p.m. Where: Technology Pavilion (Booth 880). Access: Free.

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Innovation

Microneedles Put Drug Behind Retina

By using a microneedle that is just long enough to penetrate the sclera in rabbits, researchers have found a possible way to deliver a sustained-release anti-VEGF medication to the choroid, with minimal invasiveness and without overdosing other ocular structures.1

The researchers, based at the Georgia Institute of Technology and Emory University, found that fluid injected just under the sclera with a 33-gauge needle, 750 µm long, quickly spreads in a circumferential layer between the sclera and the choroid, into what is known as the suprachoroidal space (SCS).

Drug delivery. Injected test particles persisted in the SCS for as long as two months—an indication that medication encapsulated in biodegradable particles could be slowly released there for as long as several months, the group reported.

For clinicians, better targeting of anti-VEGF drugs for macular degeneration and other neovascular diseases could reduce dosages and injection frequency, and prevent complications elsewhere in the eye, said Henry F. Edelhauser, PhD, professor in the Research (Basic Science) Section at Emory.

By contrast, “When you inject these drugs intravitreally, they have to diffuse across the neural retina, the pigment epithelium, and Bruch’s membrane, and then they get to the choroid,” he said, adding, “but the SCS is like a suprachoroidal highway for drugs to get to the back part of the eye.” 

The researchers reported the following: 

  • SCS injections succeeded in delivering fluorescent molecules to the targeted chorioretinal tissues. The concentration ratio between the chorioretinal region and the vitreous/lens interface peaked at 200:1 for sodium fluorescein, five minutes after the injection.
  • When injected intravitreally, however, the fluorescein concentration ratio never exceeded 1:1.
  • Fifteen minutes after an injection into the SCS, fluorescently tagged bevacizumab (Avastin) migrated into the chorioretinal region, with a selectivity ratio of 100:1 (compared with the vitreous/lens interface). The ratio never fell below 10:1.
  • The drug’s intraocular half-life was 7.9 ± 0.5 hours.

The needle. Previously, a different group had reported on delivering medication to the choroid using a more invasive technique, which began with surgical cutdown of the sclera and required cannulation parallel to the choroid in order to deliver a drug to the macular region.2 

But the Georgia investigators’ microneedles are sized to penetrate the sclera orthogonally, and the tiny wound is undetectable an hour later, according to the report.

Dr. Edelhauser credits a serendipitous accident for the group’s novel direction. “This is a case where you never could have written a hypothesis that you’re going to inject something into the suprachoroidal space—because we didn’t know it was even possible to do that,” Dr. Edelhauser said.

The original goal was to inject depots of sustained-release drug into the sclera. But then chemical engineer Samirkumar Patel, PhD, had a lucky accident.

“He had performed a whole series of scleral depot injections and mentioned to me that with one of the eyes the needle had gone too far, past the sclera, and all the fluorescent beads he was injecting disappeared into the back part of the eye,” Dr. Edelhauser recalled. “I told him, ‘You don’t know what door you just opened—a door to getting therapeutic drugs to the back of the eye, behind the retina.’”

—Linda Roach 

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1 Patel SR et al. Invest Ophthalmol Vis Sci. 2012;53(8):4433-4441.

2 Olsen TW et al. Am J Ophthalmol. 2006;142(5):777-787.

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Drs. Edelhauser and Patel own equity in Clearside Biomedical. Dr. Edelhauser also serves on the scientific advisory board of Alcon and is a consultant to LensAR.

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Retina Report

Early Treatment May Be Key for Wet AMD

If a retrospective Austrian study is any indication, the optimal window of opportunity for treating wet age-related macular degeneration (AMD) with ranibizumab may be narrower, and earlier, than once suspected.1

Based on duration of visual symptoms, such as distortion, changes in color vision, or central blurring, researchers assigned 45 patients with wet AMD to one of three groups: symptoms lasting less than one month; one to six months; and longer than six months. Patients received intravitreal injections of 1.25 mg of ranibizumab at baseline and after four weeks; they were evaluated for best-corrected visual acuity (BCVA) and underwent clinical exam and optical coherence tomography (OCT) at baseline and two months later.

“Only patients with symptoms for less than one month had significant gains in visual acuity, said coauthor Birgit Weingessel, MD, senior physician in the department of ophthalmology at Hietzing Hospital in Vienna. “So beginning therapy early seems to be crucial.” Patients in the second group showed an insignificant gain in BCVA, and those in the third group experienced only slight improvements.

A decrease in central retinal thickness (CRT) without a corresponding significant visual improvement underscores the lack of a one-to-one correlation between anatomic and visual outcomes, said the study authors. “We need to treat patients and their symptoms and visual function, not simply OCT images,” said Dr. Weingessel.

Clinicians should explain to their patients the pathogenesis of the disease and the importance of self-testing such as with the Amsler grid, she said, particularly since patients often notice symptoms before a clinically measurable worsening of visual function. “Patients with typical symptoms like metamorphopsia should get an OCT or fluorescein angiography as early as possible and start with anti-VEGF therapy at once, if needed,” she said. “In our clinic, most patients get the first injection on the day of diagnosis.”

A study with a larger sample size, comparing different injection regimens, she added, would provide valuable reinforcement of these study results. 

—Annie Stuart 

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1 Rauch R et al. Retina. 2012;32(7):1260-1264.

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Dr. Weingessel reports no related financial interests.

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Preclinical Trials

Eyedrops for Wet AMD Clear Safety Hurdle

With positive results from a preclinical safety study in Dutch belted rabbits and fast track designation from the Food and Drug Administration (FDA), squalamine eyedrops may soon offer patients a less invasive therapy for wet age-related macular degeneration (AMD).

In a 26-week study, rabbits received either squalamine or placebo eyedrops twice a day in both eyes. Squalamine did not build up with long-term administration, suggesting a reduced risk for systemic side effects. Researchers also reported no adverse ocular toxicity—such as irritation, redness, swelling, or discharge—or signs of lens clouding, corneal opacities and deposits, or increases in intraocular pressure.1

This company news release followed closely after a poster at the May ARVO presenting results from dosing rabbits over the course of 14 days. That study also showed good tolerability with no adverse effects.2

The drug is purported to reach the posterior segment without interfering with the anterior segment, said Andreas K. Lauer, MD, chief of the vitreoretinal division of the Casey Eye Institute at the Oregon Health & Science University in Portland.

With the discovery of its antiangiogenic properties in the late 1990s, squalamine’s potential usefulness expanded beyond that of a broad-spectrum antibiotic.3 “One attractive feature of this compound is that it blocks not only the proliferation of new abnormal blood vessels but also the growth of fibrous scar tissue that accompanies neovascularization. This scarring also contributes to retinal injury and subsequent vision loss,” said Dr. Lauer, commenting on the drug’s ability to block multiple growth factors.

Squalamine was previously tested in 250 humans in an intravenous formulation for wet AMD. Although it demonstrated biologic effectiveness and improved visual acuity, the development program was suspended due to commercial challenges.4

This new program, however, offers the compound in an eyedrop formulation that can be dosed once or twice a day, said Dr. Lauer. “If found effective and safe in humans, squalamine eyedrops have the potential to change substantially the landscape for treating this condition,” he said, adding a cautionary note that eyedrops can come with their own set of challenges, including medication tolerance and patient noncompliance.    

—Annie Stuart 

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1 http://ohrpharmaceutical.com/index-3a.html. Scroll to find “Ohr Pharmaceutical Announces Positive Preclinical Safety Study Results for Squalamine Eye Drop for Wet AMD.” Accessed Aug. 23, 2012.

2 Taraporewala IB et al. A novel eye drop formulation of squalamine for exudative AMD: evaluation of ocular distribution and ocular safety in rabbits. Presented at: Annual Meeting of the Association for Research in Vision and Ophthalmology; May 6, 2012; Fort Lauderdale, Fla. Poster #D1134.

3 Higgins RD et al. Invest Ophthalmol Vis Sci. 2000;41(6):1507-1512.

4 http://ohrpharmaceutical.com/index-2d.html. Accessed Aug. 23, 2012.

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Dr. Lauer reports no related financial interests.

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Glaucoma Report

Fruits, Vegetables May Lower Glaucoma Risk

A cross-sectional research study conducted in conjunction with the Study of Osteoporotic Fractures Research Group has yielded valuable insights into the risk of glaucoma among older African-American women.

“Eating fruits and vegetables high in vitamin A, vitamin C, and carotenoids is associated with lower rates of glaucoma, according to the report.1 No doubt there are other as-yet unknown factors involved, supporting the recommendation that patients eat more fruits and vegetables—specifically, oranges, peaches, kale, and collard greens,” said Anne L. Coleman, MD, PhD, a study coauthor and professor of ophthalmology at the Jules Stein Eye Institute at UCLA, and professor of epidemiology in the UCLA Fielding School of Public Health. 

In the study, disc photographs and suprathreshold visual fields were obtained from the 662 African-American participants in the Study of Osteoporotic Fractures. The Block Food Frequency Questionnaire was used to assess food consumption. Relationships between glaucoma and summaries of fruit/vegetable consumption were evaluated using logistic regression models.

Glaucoma was diagnosed in at least one eye of 13 percent of study subjects. Participants who ate three or more servings per day of fruits and/or fruit juices were 79 percent less likely to have glaucoma than participants who ate less than one serving per day. Women who consumed more than two servings per week of fresh oranges and peaches had lower odds of glaucoma than did those who had less than one serving. As for vegetables, more than one serving weekly of collard greens or kale was associated with 57 percent lower odds of glaucoma, compared with one serving or less per month.

“As a scientist, I’d like confirming evidence to show that these foods are beneficial, such as a prospective study showing similar results. But as a clinician, I’m pleased to have something to offer patients and their families so that they can play a more active role in their own care,” said Dr. Coleman.

—Laura B. Kaufman 

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1 Giaconi JA et al. Am J Ophthalmol. Published online July 20, 2012.

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Dr. Coleman has received funding for her work from the NEI/NIH.

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