American Academy of Ophthalmology Web Site: www.aao.org
New Findings from Ophthalmology, AJO and Archives
April’s American Journal of Ophthalmology:
February’s Archives of Ophthalmology:
Roundup of Other Journals:
Ranibizumab Alone or in Combination With Laser Is Superior to Laser Monotherapy for Diabetic Macular Edema
Mitchell et al. showed that treatment with ranibizumab—whether as monotherapy or combined with laser treatment—is superior to laser treatment alone in terms of rapidly improving and sustaining visual acuity in patients with diabetic macular edema (DME).
The 12-month study involved 345 patients with diabetes mellitus and visual impairment due to DME. The authors randomized 116 patients to ranibizumab plus sham laser, 118 to ranibizumab plus laser and 111 to sham injections plus laser. Treatment with ranibizumab alone or combined with laser proved superior to laser monotherapy in improving the mean average change in BCVA from baseline through month 12.
By month 12, a significantly larger proportion of patients treated with ranibizumab alone or in combination with laser had a BCVA letter score of greater than or equal to 15 and a BCVA letter score level of greater than 73. In addition, quality of life improved significantly during the study period for patients who received either of the ranibizumab treatments. Ranibizumab consistently improved BCVA across all patient subgroups, including patients with focal or diffuse DME.
Fluocinolone acetonide (FA) intravitreal inserts are nonbiodegradable cylindrical tubes that are loaded with FA and do not require a surgical operation for implantation. Instead, the device is inserted into the vitreous cavity through a 25-gauge needle in an outpatient clinic. In this report, Campochiaro et al. reported findings of two parallel prospective, randomized, phase 3 studies testing the effects of FA inserts in patients with persistent diabetic macular edema (DME) who had undergone at least one macular laser treatment.
The authors randomized 185 patients to sham injection, 375 to a low-dose (0.2 µg/day) insert and 393 to a high-dose (0.5 µg/day) insert. They report that patients demonstrated significant improvement in BCVA with both low- and high-dose FA inserts over two years, with the risk/benefit ratio being superior in the low-dose device.
The FDA has requested an additional year of data before considering approval for this drug-delivery system.
Price et al. showed that the five-year Descemet’s stripping endothelial keratoplasty (DSEK) graft survival rate compares well with previously reported penetrating keratoplasty (PK) five-year survival rates for Fuchs dystrophy and pseudophakic or aphakic corneal edema. In addition, the endothelial cell loss in DSEK grafts that survive five years compares favorably with the five-year cell loss in PK grafts performed to treat similar moderate risk conditions in the Cornea Donor Study.
This retrospective case series involved 165 eyes of 149 patients treated with primary DSEK. The cumulative five-year survival rate was significantly lower for pseudophakic or aphakic eyes with corneal edema (76 percent) than it was for Fuchs eyes (95 percent). The five-year survival rate was reduced significantly in eyes with a prior glaucoma shunt or trabeculectomy surgery. The five-year endothelial cell loss after DSEK was 53 percent compared with 70 percent measured after PK in the Cornea Donor Study.
The authors conclude that these five-year findings indicate the technique is a viable alternative for treating endothelial dysfunction.
American Journal of Ophthalmology
In a randomized, double-masked, multicenter clinical trial, Krupin et al. compared the alpha2-adrenergic agonist brimonidine tartrate 0.2 percent to the beta-adrenergic antagonist timolol maleate 0.5 percent in preserving visual function in low-pressure glaucoma.
Exclusion criteria included the following: a history of IOP of greater than 21 mmHg; BCVA worse than 20/40 in either eye; a history of angle closure or an occludable angle by gonioscopy; prior glaucoma incisional surgery; inflammatory eye disease; prior ocular trauma; diabetic retinopathy or other diseases capable of causing visual field loss or optic nerve deterioration; extensive glaucomatous visual field damage with a mean deviation worse than –16 dB; or a clinically determined threat to central fixation in either eye.
Standard automated perimetry and tonometry were performed at four-month intervals. The main outcome measure was field progression in either eye—defined as the same three or more points with a negative slope of greater than –1 dB/year.
The researchers randomized 99 patients to brimonidine and 79 to timolol; both eyes received twice-daily monotherapy. Mean follow-up for all patients was 30 months. Fewer brimonidine-treated patients had visual field progression by pointwise linear regression than timolol-treated patients. Mean treated IOP was similar for brimonidine- and timolol-treated patients at all time points. More brimonidine- treated than timolol-treated patients discontinued study participation because of adverse events.
The authors conclude that low-pressure glaucoma patients treated with brimonidine 0.2 percent who do not develop ocular allergy are less likely to have field progression than patients treated with timolol 0.5 percent.
Shimura et al. evaluated the effectiveness of preseasonal treatment with topical olopatadine on the reduction of clinical symptoms of seasonal allergic conjunctivitis.
Eleven patients with seasonal allergic conjunctivitis received topical olopatadine in one eye at least two weeks before the onset of allergy symptoms; the other eye served as the control. After the onset of allergic conjunctivitis, both eyes were treated with topical olopatadine. The researchers measured the tear levels of histamine and substance P up to six weeks, and used a visual analogue scale (VAS) to evaluate the subjective symptoms of ocular allergy.
At the onset of allergy symptoms, the VAS score in the pretreatment eyes was significantly lower than that in the control eyes. The VAS score in the control eyes decreased with time, but it did not decrease to the level seen in the pretreatment eyes until four weeks later. The tear level of substance P at the onset of allergy symptoms was significantly suppressed in the pretreatment eyes, while the level of histamine was not suppressed. Alteration of the VAS scores in the pretreatment eyes significantly correlated with the level of substance P—but not the level of histamine.
In a prospective, randomized clinical trial, Simon et al. compared treatment outcomes of intralesional triamcinolone acetonide (TA) injection with incision and curettage for primary chalazia.
The authors randomized 94 patients with primary chalazia who failed conservative treatment to either intralesional TA injection or incision and curettage performed under local anesthesia. All patients underwent comprehensive eye examinations that included digital photography of the lesion. Complete resolution was defined as lesion regression of 95 to 100 percent. Treatment was considered a failure if no resolution was achieved after the first attempted incision and curettage or first TA injection.
Forty-two patients underwent incision and curettage and 52 underwent TA injection. Thirty-three patients (79 percent) in the incision and curettage group and 42 patients (81 percent) in the TA group achieved complete resolution. The average time to resolution in the TA group was five days. TA precipitates were detected in six patients (11.5 percent) and resolved spontaneously. There were no complications—such as eyelid depigmentation, increased IOP or any loss of vision—in either group.
The authors conclude that intralesional TA injection is as effective as incision and curettage in treatment of primary chalazia. Injection may be considered as an alternative first-line treatment in cases where diagnosis is straightforward and no biopsy is required.
Archives of Ophthalmology
Bullock et al. investigated the effects of time, temperature and container properties on the ability of ReNu with MoistureLoc (ReNuML) to inhibit growth of Fusarium species. They found that, when exposed to elevated storage temperature, an interaction between ReNuML and its Bausch & Lomb plastic container adversely affected the fungistatic properties of ReNuML—which could have contributed to the Fusarium keratitis epidemic of 2004–2006.
The researchers stored ReNuML in its Bausch & Lomb plastic or similarly-sized glass containers for one and four weeks at room temperature, 42 degrees C and 56 degrees C. They then tested for its ability to inhibit growth of seven Fusarium isolates.
ReNuML stored in glass containers for one or four weeks at all three temperatures demonstrated no significant fungistatic deterioration. However, ReNuML stored at 56 degrees C in its Bausch & Lomb plastic container demonstrated a statistically significant fungistatic deterioration compared with room temperature storage in its original plastic container or with glass container storage at any temperature.
Patient-Reported Outcomes Among Sham and No-Treatment Controls
Hawkins et al. retrospectively compared sham and no-treatment control-arm patients from two randomized trials treating subfoveal choroidal neovascularization secondary to age-related macular degeneration.
The comparison was based on two-year change in vision-targeted quality of life, as measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ). A total of 62 pairs of no-treatment and sham controls were matched on seven criteria associated with changes in NEI- eyenet 23 Journal Highlights VFQ scores; matching criteria included the baseline NEI-VFQ overall score.
When two-year changes in scores were compared, no important difference in either overall NEI-VFQ scores or subscale scores was found. Because of the small number of control pairs that could be matched, the confidence interval on mean differences in changes was wide (-33 to +34).
The authors conclude that sham treatments to mask patient participants in clinical trials in which patient-reported outcomes are of interest may not be necessary as long as other methods of minimizing outcome assessment bias are incorporated into the trial design.
In a prospective case series, Kotecha et al. examined the efficacy of intravitreal bevacizumab for pain relief in eyes with refractory neovascular glaucoma.
Fifty patients (52 eyes) with refractory neovascular glaucoma were administered 1.25 mg bevacizumab and followed for six months. The authors measured the subjective pain score at each visit and evaluated IOP and iris neovascularization. Surgical intervention for IOP control was performed according to clinical need.
Forty-two patients (44 eyes) completed the six-month follow-up. Subjective pain score was significantly lower one week following the injection and lasted throughout the follow-up period. A rapid, yet relatively transient, reduction in iris neovascularization was also noted. Four eyes (8 percent) required more than one injection to facilitate intraocular surgery. The authors comment that while the long-term pain relief experienced by patients might be explained by overall IOP reduction, the immediate pain relief was attributable to the use of bevacizumab.
The authors conclude that bevacizumab is a useful adjunct in the management of refractory neovascular glaucoma, offering rapid pain relief and regression of iris neovascularization. However, they comment that their study did not suggest it should replace panretinal photocoagulation. The authors found no evidence to suggest that bevacizumab lowers IOP in eyes with angle closure and report that conventional medical, laser and surgical treatment is still needed in these eyes.
Takihara et al. examined whether previous phacoemulsification adversely affects surgical prognosis of trabeculectomy with mitomycin for open-angle glaucoma.
The authors retrospectively evaluated 226 patients with open-angle glaucoma undergoing trabeculectomy with mitomycin at two clinical centers. The patients were divided into two groups: 175 phakic eyes (phakic group) and 51 pseudophakic eyes that had undergone phacoemulsification with superior conjunctival incision. The authors compared surgical success between the two groups. Success was defined as the ability to maintain IOP levels below the upper limits of 21, 18 or 15 mmHg without an additional glaucoma surgery.
Kaplan-Meier survival-curve analysis revealed that the pseudophakic group was less successful than the phakic group. The Cox proportional hazards model confirmed that previous phacoemulsification independently contributed to surgical failure of trabeculectomy.
The authors conclude that previous phacoemulsification is a prognostic factor for surgical failure of trabeculectomy with mitomycin for open-angle glaucoma.
Roundup of Other Journals
Given that tears serve as a chemosignal in mice, Gelstein et al. hypothesized that human tears may serve a similar function.
The researchers had male participants view images of emotionally ambiguous women’s faces and asked them to rate each face’s sexual appeal. Each man viewed the images twice, once while sniffing saline and once with odorless tears contributed by women experiencing negative emotions. The researchers found a shift in sexual appeal attributed to the faces, whereby the faces appeared less attractive after sniffing tears than after sniffing saline.
Moreover, after sniffing such tears, men experienced reduced self-rated sexual arousal, reduced physiological measures of arousal and reduced levels of testosterone. Functional magnetic resonance imaging in these men revealed selectively reduced activity in brain substrates of sexual arousal. These effects were observed even though participants did not actually see women cry, nor did they know where the tears came from.
Wang et al. found an association between a thick iris and angle closure.
The researchers recruited a broad group of angle-closure patients with both primary angle closure (PAC) and primary angle-closure glaucoma (PACG) from glaucoma clinics at a tertiary eye hospital in Singapore. Both PAC and PACG patients, along with controls, were examined with anterior segment OCT that utilized customized software to measure iris thickness. The scans measured iris thickness at 750 µm (IT750) and 2,000 µm (IT2000) from the scleral spur, maximal iris thickness (ITM) and the cross-sectional area of the iris (I-Area).
After adjusting for age, sex, pupil size and anterior-chamber depth, the mean values of IT750, IT2000, ITM and I-Area were significantly greater in the angle-closure patients than the controls. On the other hand, the iris curvature was greater in controls.
The authors note that their results were consistent among all three iris-thickness positions (IT750, IT2000 and ITM).
Kankipati et al. showed a significant reduction in post-illumination pupil response (PIPR) in patients with glaucomatous optic neuropathy (GON) and demonstrated a correlation between reduced PIPR and the severity of visual field loss.
The study involved 17 patients with glaucoma and 19 age-matched controls. PIPR was tested with a 60-degree, 10-second light stimulus of either blue or red to one eye after dilation. The consensual pupil response of the fellow, undilated eye was recorded by infrared pupillometry for 50 seconds after light offset. Patients with glaucoma demonstrated a net PIPR (blue minus red) that was significantly smaller than in age-matched controls. In addition, the size of the net PIPR was inversely correlated with the measured field loss of the tested eye.
The authors assert that measuring PIPR may represent a viable method for detecting glaucoma.
Roundup of Other Journals is written by Lori Baker Schena, PhD, and edited by Deepak P. Edward, MD.