Research highlights of ARVO 2014

Presentations shed new light on transplant tissues, pattern dystrophy and other ocular science.

By the Editors of Ophthalmology Management

Each year, the annual ARVO meeting offers a mother lode of new information. This year, ARVO accepted 6,445 papers and presentations covering the range of ophthalmic research. Having spent numerous hours painstakingly sifting through the abstracts for many of these presentations, our editors have come up with six relevant presentations we highlight here.

Disqualified corneas may be suitable for transplant

Donor corneal tissue may be discarded unnecessarily in some cases, a pilot study from the Lion’s Eye Institute for Transplant and Research (LEITR) and the University of Florida has suggested.¹ The study looks at corneal tissues from donors with positive sputum cultures before death. The investigators harvested corneoscleral rims postmortem and placed them in a cold environment for five days. The corneas had been disqualified for transplant due to low endothelial cell counts. After the five-day period, the researchers observed no growth of either bacteria or fungi. The samples were negative for growth even after the researchers extended the incubation time for fungal cultures for three weeks.

“It was very encouraging,” says Mitchell McCartney, PhD, of LEITR. He says, pending results from a wider study, this research may lead to a dramatic shift in eye bank qualification criteria. “When we expand the study, on the premise that it continues to show these results, it will give us confidence” to use the tissue from donors who had positive sputum cultures, he says. “The surgeons can be assured there isn’t going to be cross contamination.”

The concept for the study developed after a discussion about donor acceptability. “We said, ‘It would be really nice to have some objective data to easily be able to rule those people in if we could prove that positive sputum wasn’t transferring in the rim cultures,’ ” Dr. McCartney says.

For patients with corneal complications such as Fuch’s endothelial dystrophy or keratoconus, transplant surgeons err on the side of caution, Dr. McCartney says. Often, donor tissue positive for fungi or, to a slightly lesser degree, bacteria won’t be accepted for fear of potential cross contamination that could result in graft failure, he explains. However, many of these suspicions have never been fully tested, he says.

This research looked at 18 corneas — “not statistically significant” in Dr. McCartney’s words. However, the strong findings of this pilot study are significant enough to warrant a larger study, he says. An additional next step is to evaluate the potential for cross-contamination of MRSA. “When you get resistant bacteria, people get really concerned,” Dr. McCartney says.

Misdiagnosis of pattern dystrophy as AMD

Researchers led by Voraporn Chaikitmongkol, MD, of the Wilmer Eye Institute, set out to determine the frequency that clinicians misdiagnosed pattern dystrophy of the retinal pigment epithelium (RPE) as AMD.² Distinguishing pattern dystrophy from AMD is one of the most difficult differential diagnoses a retina specialist has to make.

The researchers first identified patients, based on ICD-9 codes, of two retina specialists at a university-based practice over eight years who had AMD or retinal dystrophies. Dr. Chaikitmongkol and Neil M. Bressler, MD, retrospectively reviewed the cases to identify those with a pattern dystrophy of the RPE as confirmed by fundus photographs and, when available, fluorescein angiograms. The researchers also reviewed medical records and referral letters of those patients with a confirmed diagnosis of pattern dystrophy to determine if the previous diagnosis was AMD.

The researchers eventually reviewed 1,092 patient records, among which 86 had a diagnosis of pattern dystrophy of the RPE. Subsequent review confirmed 64 with pattern dystrophy and no large drusen (pattern dystrophy and no AMD). Seventeen additional cases had pattern dystrophy with at least one large druse in either eye (pattern dystrophy and AMD).

Of the 64 cases that had pattern dystrophy but no AMD, 36 were referred initially as having AMD. Among these 36 patients, the median age was 69 years, 67% were women, 97% were Caucasian and 75% had pattern dystrophy in both eyes. Also among these 36 patients (61 eyes), the median presenting visual acuity was 20/40. Seven eyes had geographic atrophy involving the fovea; four had geographic atrophy not involving the fovea; and four had choroidal neovascularization (all received anti-VEGF therapy).

None of the other 32 misdiagnosed patients received anti-VEGF therapy. Eleven of the 36 misdiagnosed patients were taking dietary supplements for AMD. All 11 were advised to consider discontinuing the supplements.

The researchers concluded that while pattern dystrophy of the RPE is far less common than AMD, most pattern dystrophy cases appear to be misdiagnosed as AMD, which could impact physician-patient discussions regarding diagnosis, prognosis and management.

Experience with trauma-induced cataracts

Trauma-induced cataracts, such as those contusions or other blunt-force injuries cause, can result in almost total vision loss, but a study of the treatment of these cataracts demonstrated that functional vision can be restored in a majority of patients.⁴

Researchers at the Oftalmologia Instituto Oftalmologia Conde Valenciana in Mexico conducted a retrospective review of 80 patients treated for traumatic cataract at the facility in a two-year period between 2010 and 2012. Sixty-seven patients were men and the mean age at presentation was 46 years. Time between trauma and the initial consult was a mean of one year but covered a wide range from four hours to 63 years.

Patients’ BCVA upon presentation ranged from 20/30 to light perception, with a mean of 3/200. Total white cataract from closed-globe trauma was the common morphology, accounting for almost half of the cases. Seventy-seven of the 80 eyes were managed with phacoemulsification, with 11 requiring capsular tension rings and 18 anterior automated vitrectomy. In 42 cases, surgeons implanted an in-the-bag IOL.

Final BCVA was a mean of 20/30, with outcomes ranging from 20/20 to light perception. Forty-seven patients achieved final BCVA of 20/40 or better.

The researchers concluded phacoemulsifaction with in-the-bag IOL was the most effective treatment for the great majority of these cases, and that this approach could achieve 20/40 BCVA or better in a majority of cases.

Dexamethasone delivers with fewer injections

Twelve-month results from a two-year clinical trial comparing bevacizumab (Avastin, Genentech, South San Francisco, Calif.) and dexamethasone (Ozurdex, Allergan, Irvine, Calif.) for persistent DME showed that dexamethasone “generally achieved better anatomical outcomes” with 2.8 injections in one year vs. 8.8 for bevacizumab.³

The phase 2, prospective, multicenter, randomized, single-masked study looked at 88 eyes of 61 patients in four Australian sites. Forty-two eyes received intravitreal injections of bevacizumab, while 46 eyes received dexamethasone sustained-release implants, both PRN.

The primary outcome was the proportion of eyes that improved by 10 LogMAR letters; secondary outcomes included mean change in VA, central macular thickness (CMT), frequency of injection and adverse events.

The researchers reported that gains in VA did not differ significantly between the two groups. VA improvements of 10 or more letters were found in 17 of 42 eyes treated with bevacizumab compared with 18 of 46 dexamethasone-treated eyes. None of the bevacizumab eyes lost 10 or more letters, but 11% of dexamethasone eyes did, “mostly due to unoperated cataract,” according to the study. The mean improvement in VA was 8.9 letters for bevacizumab eyes vs. 5.6 letters for dexamethasone eyes. As for mean CMT at 12 months, it was “significantly greater” for bevacizumab eyes than for dexamethasone eyes (380.6 μm vs. 285 μm).

Lead author, Mark C. Gilles, PhD, University of Sydney, says he does not favor a combination approach using the two drugs, because dexamethasone is sufficient to treat DME, while adding an anti-VEGF to dexamethasone does not add value.

Sustained-release of steroid from a punctum plug

A multi-practice, 60-patient study evaluated the performance of a punctum plug (Ocular Therapeutix, Bedford, Mass.) in effectively delivering the steroid dexamethasone as a treatment for pain and inflammation following cataract surgery when placed in the vertical canaliculus of the eye.⁵ The plug was designed to release dexamethasone into the tear film in a tapered manner over a 30-day period.

The study involved two groups, each comprising 30 patients, with one group receiving the plug containing dexamethasone and the other a placebo vehicle punctum plug (PVPP) inserted into the canaliculus of the operated eye at the conclusion of cataract surgery. The PVPP was identical to the dexamethasone plug but without the drug. Over 30 days, patients were monitored for ocular pain and inflammation (anterior chamber cells and aqueous flare). Plug retention was assessed using a slit lamp.

Over the study duration, the investigators found more patients who received the dexamethasone plug showed an absence of cells compared to the PVPP group. This difference was most significant at days 14 and 30.

At all study intervals, the absence of ocular pain and anterior chamber aqueous flare was significantly lower for the dexamethasone plug. The amount of aqueous flare and cells in the anterior chamber is indicative of increased protein content and inflammatory cells are a sign of intraocular inflammation. Dexamethasone plug retention was 100% through 14 days and 97% at day 30, and was considered easy to visualize with a slit lamp.

The researchers concluded that a single dose of sustained-release dexamethasone at the time of surgery can be a convenient administration option to ensure treatment, especially when compared to the demanding dosing regimen for topical administration. Clinical results demonstrated pharmacodynamic performance as indicated in the relief of postoperative pain and reductions in the key ocular inflammatory markers of both cells and flare.

Low incidence of endophthalmitis after vitrectomy

British researchers led by Jonathan C. Park, MD, of the Royal Devon and Exeter Hospital conducted the first nationwide prospective study to investigate the incidence and risk factors following pars plana vitrectomy. The study also aimed to provide epidemiological data relating to clinical presentation, microbiology, management and outcome of endophthalmitis following vitrectomy.⁶

Cases of presumed infectious endophthalmitis within six weeks of pars plans vitrectomy were reported via the established British Ophthalmological Surveillance Unit. The surveillance period was two years. Controls (patients who had vitrectomy but no endophthalmitis) were recruited from nine randomly selected UK centers.

Thirty-seven reports were received and 28 cases met the diagnostic criteria for presumed infectious endophthalmitis following vitrectomy. The incidence of endophthalmitis following vitrectomy was 28 cases per 48,433 vitrectomies (1:1,730).

Two hundred and seventy-two controls were randomly recruited from nine UK centers. Smaller-gauge port sizes were not found to be a risk. Immunosuppression and preoperative topical steroids increased the endophthalmitis risk. Surgery for retinal detachment was associated with a reduced risk of endophthalmitis. Mean age was 61 years and 67% were men. Nineteen cases involved 23/25 gauge instruments and nine cases utilized 20-gauge.

Mean time from surgery to endophthalmitis was five days. Blurred vision (85.2%), pain (77.8%) and a hypopyon (77.8%) were the most common presenting symptoms and signs. Seventeen cases (60.7%) had a positive culture. Culture-positive endophthalmitis, relative to culture-negative endophthalmitis, was no different with respect to time to presentation, symptoms, signs or outcome. Outcome was poor with 29.6% of eyes being eviscerated or having no perception of light or perception of light.

The researchers concluded that endophthalmitis following vitrectomy is rare. Operating with smaller-gauge port sizes does not increase the risk of endophthalmitis. The findings may help surgeons promptly identify cases of endophthalmitis following vitrectomy and inform them about the various management options available and the likely outcome of this devastating complication. OM

REFERENCES