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Journal Highlights
New Findings from Ophthalmology, AJO, and Archives
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American Journal of Ophthalmology:

Archives of Ophthalmology:

Roundup of Other Journals:



Liver Function Tests to Detect Early Metastasis in Uveal Melanoma Patients
August’s Ophthalmology

In a retrospective study, Mouriaux et al. evaluated whether liver function tests (LFTs) can detect early liver metastasis in patients with uveal melanoma. They found that isolated or combined LFTs for aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase, lactate dehydrogenase, and alkaline phosphatase are not helpful for detection of early metastasis. However, the negative predictive value of these tests was high (90 percent or greater), giving physicians the ability to reassure patients when the LFT results are negative.

For this study, the authors used the data bank from their Canadian institution and included 88 patients with uveal melanoma in whom metastasis developed during semiannual follow-ups with LFTs. The authors also included 174 patients with uveal melanoma without metastasis as controls. For each test, they estimated sensitivity, specificity, positive predictive value, and negative predictive value from cross-tabulation tables of test results according to the diagnosis of metastasis. They then utilized log-binomial regression models to compare proportions of false-positive results between groups of patients with and without metastasis.

Metastases were detected after LFT abnormality (at least one abnormal test result) in 40 patients (45 percent). The overall sensitivity of the LFTs ranged from 12.5 percent to 58 percent, and the positive predictive value ranged from 9.4 percent to 38.6 percent. The overall specificity and negative predictive values for the different LFTs were 90 percent or greater. The proportions of false-positive results between groups of patients with and without metastasis did not differ significantly. Using Canadian dollars, the authors found that semiannual screenings with LFTs cost $35.50 per year per patient in Quebec, which included liver imaging prompted by positive and false-positive results. They noted this cost could vary greatly from one country to another.

The authors recommended conducting a prospective study to confirm their results.


SiRNA PF-04523655 Alone and in Combination With Ranibizumab for AMD

Published online June 11, 2012

Nguyen et al. conducted an exploratory study evaluating the efficacy of PF-04523655 (PF), a small interfering RNA, as monotherapy or in combination with ranibizumab for the treatment of age-related macular degeneration (AMD). They found that combining PF with ranibizumab led to a larger gain in BCVA than did ranibizumab alone.

This phase 2, multicenter, open-label, prospective study included 151 patients with subfoveal choroidal neovascularization (CNV) secondary to AMD who had never been treated for the condition.

The researchers randomized patients to one of five treatment groups: Group 1 received 1 mg of PF every four weeks from week 4 to week 12; group 2 received 3 mg of PF every four weeks from week 4 to week 12; group 3 received 3 mg of PF every two weeks from week 4 to week 12; group 4 received 1 mg of PF together with 0.5 mg of ranibizumab every four weeks from baseline to week 12; and group 5 received 0.5 mg of ranibizumab alone every four weeks to week 12. All groups received 0.5 mg of ranibizumab at baseline, and all treatments were given as intravitreal injections.

PF treatment appeared generally safe, with few mild or moderate adverse events. No severe events were attributed to study treatment. Although the combination PF/ranibizumab and  ranibizumab monotherapy groups both showed continued improvement after week 4, the combination group experienced a numerically greater mean change in both BCVA letters and  proportion of patients who gained at least 10 or 15 letters. Mean change in BCVA letters in all

PF monotherapy groups was less than in the ranibizumab monotherapy group. From baseline to week 16, the combination PF/ranibizumab and ranibizumab monotherapy groups had similar mean reductions in central subfield retinal thickness and total CNV area, which were greater than in all PF monotherapy groups. No clinically meaningful differences were seen in reduction of lesion thickness among treatment groups.

The researchers concluded that further studies should be conducted to evaluate long-term safety and optimal dosing of PF, both alone and in combination with other therapies.


Corneal Collagen Cross-Linking With Transepithelial Phototherapeutic Keratectomy

Published online June 8, 2012

Kymionis et al. compared the outcomes of corneal collagen cross-linking for the treatment of progressive keratoconus using two different techniques for epithelial removal: transepithelial phototherapeutic keratectomy (t-PTK) and mechanical epithelial debridement. They found that the former provides better visual and refractive outcomes.

This prospective, comparative, interventional case series involved 34 patients (38 eyes). No intraoperative or postoperative complications were observed in any of the patients, and no alterations in endothelial cell density occurred during the 12-month follow-up period in either of the two treatment groups.

According to the authors, the goal of using t-PTK was to decrease the keratoconus-induced irregular astigmatism via epithelial removal and smoothing of the anterior corneal stroma. Results showed that after corneal collagen cross-linking with t-PTK, patients experienced a significant improvement in visual acuity and mean steep keratometric readings. Similar results were not seen in patients who underwent the mechanical epithelial debridement: Improvement in visual acuity did not attain significance at any postop interval, and mean steep keratometric readings did not change significantly during the follow-up period.

The researchers called for a larger study with longer follow-up to better determine the outcomes of the t-PTK procedure.


Correction of Refractive Error in Latinos Not Sufficient for Distance Visual Function

Published online June 8, 2012

In a study of 4,272 Latinos over age 40, Sandhu et al. assessed the relationship between correction of myopia, hyperopia, and astigmatism, and self-reported near and distance visual function. They found that correction of any type of refractive error (RE) is not entirely sufficient to restore distance visual function to the level of those without RE.

In this population-based, cross-sectional study, the authors defined cases of RE as having at least one of the following criteria in both eyes: myopia, sphere correction of –0.5 D or less; hyperopia, sphere correction of 1 D or more; or astigmatism, cylinder of 0.75 D or more. The authors defined uncorrected refractive error (URE) as having an RE and achieving two or more lines of improvement in visual acuity in both eyes after refraction. Of the 4,272 participants, 2,307 (54 percent) had RE. Of these individuals, 14 percent of myopes, 21 percent of hyperopes, and 22 percent of astigmatics had URE.

The authors found that individuals with myopia, hyperopia, or astigmatism were significantly more likely to report difficulty with distance vision than subjects without refractive error, regardless of whether they had correction. Individuals with corrected myopia reported less difficulty with near vision than individuals without RE. Those with uncorrected hyperopia and uncorrected astigmatism reported more difficulty with near vision than those without RE. Self-reported distance and near visual function scores were sensitive to nonvision variables, namely, age, sex, diabetes, blood pressure, acculturation score, income, and education.

The investigators concluded that these findings are of particular importance, given the large Latino population in the United States. They recommended that more research should be conducted to better understand the underlying reasons why Latino individuals experience ongoing dissatisfaction in distance visual function after correction of refractive error.


American Journal of Ophthalmology

Depression, Stress, and Dry Eye Syndrome
August’s AJO

Using the national United States Veterans Affairs administrative database, Galor et al. studied the scope of dry eye syndrome (DES) in veterans and evaluated its relationship with psychiatric diagnoses. They found that DES is associated with depression and posttraumatic stress disorder and is prevalent among male and female veterans receiving eye care services.

The authors divided patients into cases and controls according to their dry eye status. The main outcome measures were prevalence of DES and influence of psychiatric diagnoses on the risk of DES. They identified a total of 2,454,458 patients as either a dry eye case (462,641) or control (1,991,817). Overall, 19 percent of male patients and 22 percent of female patients had a diagnosis of DES, with female sex imparting an increased risk of DES at each decade compared with male sex. The authors identified several conditions that increased DES risk, including posttraumatic stress disorder and depression. The use of several systemic medications was likewise associated with an increased risk of DES, including antidepressant and antianxiety medications. Multivariate analysis examining the relationship between medical diagnoses and use of relevant systemic medications revealed that for psychiatric diagnoses, both the use of medication and the diagnosis remained significant risk factors for DES; however, the magnitude of each association decreased when both factors were analyzed concomitantly.

The authors noted that the association between DES and these psychiatric conditions could be driven by underlying disease physiology or the medications used to treat psychiatric conditions. Regardless of the causal link, these findings suggest that individuals with a known psychiatric diagnosis should be questioned or evaluated about dry eye symptoms or signs.


The Changing Face of Primary Open-Angle Glaucoma
August’s AJO

Vajaranant et al. performed a cross-sectional study to determine how demographic and geographic variations in U.S. populations from 2011 to 2050 will contribute to estimated numbers of primary open-angle glaucoma (POAG) cases. They found that the highest prevalence of POAG in the United States is currently among older Caucasian women and is expected to shift to Hispanic men over the next few decades.

The authors used prevalence rates from selected population-based studies to estimate the number of persons aged 40 years and older with POAG in the United States. For projections, they multiplied the age-, sex-, and race/ethnicity-specific prevalence rates by U.S. Census demographic estimates from 2011 to 2050.

In 2011, 2.71 million persons in the United States had POAG, with the highest number among Caucasian women (25 percent), Caucasian men (20 percent), and populations aged 70 to 79 years (31 percent). In 2050, an estimated 7.32 million persons will have POAG, with the highest number among Hispanic men (25 percent), Hispanic women (24 percent), and populations aged 70 to 79 years (32 percent). During the next 40 years, the per capita rates of POAG will double in New Mexico, Texas, and Florida.


Surface-Light Scattering and Glistenings of IOLs
August’s AJO

Hayashi et al. investigated the long-term effect of surface-light scattering and glistenings of various IOLs on visual function and optical aberrations after cataract surgery. They found that visual function and ocular higher-order aberrations (HOAs) were comparable among eyes that received acrylic, silicone, and polymethyl methacrylate (PMMA) IOLs. They also found that the surface-light scattering and glistenings more commonly found with acrylic IOLs were not significantly correlated with visual function and optical aberrations.

The authors studied 35 eyes that had undergone implantation of a hydrophobic acrylic, silicone, or PMMA IOL more than 10 years ago. They measured scattering-light intensity of the surface and internal matrix of the optic using Scheimpflug photography; visual acuity (VA) using VA charts; and contrast VA and glare VA using a contrast sensitivity tester. They evaluated ocular HOAs using a Hartmann-Shack aberrometer.

The authors found that mean scattering-light intensity of the surface and internal matrix of the optic was significantly higher in the acrylic group than in the silicone and PMMA groups. Mean uncorrected VA, HOAs, and photopic and mesopic contrast VA and glare VA did not differ significantly among groups, although mean corrected VA in the acrylic group was significantly better than in the other groups. Scattering-light intensity of the surface and internal matrix did not correlate with VA, contrast VA, or glare VA and did not correlate with ocular and internal optic HOAs in the acrylic group.


Archives of Ophthalmology

Genotype-Phenotype Correlations in Bardet-Biedl Syndrome
July’s Archives

Daniels et al. evaluated whether mutations in different Bardet-Biedl syndrome (BBS) genes result in different ocular phenotypes. They found that patients with BBS1 mutations manifest a milder phenotype than patients with mutations in other BBS genes. Clinically, this presented as significantly better acuity and larger electroretinogram (ERG) amplitudes.

The authors enrolled 37 patients from 31 families who met clinical criteria for BBS and for whom a BBS mutation had been identified. Seventeen patients harbored mutations in BBS1, 10 in BBS10, and 10 in other genes (BBS2, 3, 5, 7, and 12). All patients underwent ocular examination; 36 patients had computerized full-field ERGs.

Visual acuity was significantly better among BBS1 patients than among BBS patients with other mutations. BBS1 patients produced significantly higher ERG amplitudes in response to 0.5- and 30-Hz flashes than patients with other BBS mutations. All BBS1 patients had at least one missense mutation, compared with only 45 percent of patients with mutations in other BBS genes; the rest had only null alleles. However, multivariate analysis demonstrated that visual acuity or ERG amplitude did not depend on the type of mutation present (missense or null) when controlling for BBS gene. Prevalences of bone-spicule pigmentation and cataract were comparable among BBS subtypes.


Visual Impairment, Age-Related Eye Diseases, and Cognitive Function
July’s Archives

In this study, Ong et al. explored the associations of visual impairment and cognitive function as well as the associations between age-related eye diseases and cognitive function in an older Asian population. They found that older persons with visual impairment, especially when caused by cataract, were more likely to have cognitive dysfunction. When looking at major age-related eye diseases independent of visual acuity, the authors found that only diabetic retinopathy was associated with dysfunction.

The authors examined 1,179 participants aged 60 to 80 years from the Singapore Malay Eye Study. They measured visual acuity using the logMAR vision chart. Cataract, age-related macular degeneration (AMD), and diabetic retinopathy were graded using the Wisconsin Cataract Grading System, Wisconsin Age-Related Maculopathy Grading System, and modified Airlie House classification system, respectively. Glaucoma was diagnosed using the International Society Geographical and Epidemiologic Ophthalmology criteria. The authors based their analysis of cognitive dysfunction on the Abbreviated Mental Test.

Visual impairment based on presenting visual acuity was more likely associated with cognitive dysfunction than was visual impairment based on BCVA, which could suggest a role of undercorrected refractive error in dysfunction.

Visual impairment caused by cataract was also significantly associated with an increased risk of cognitive dysfunction. In contrast, the authors did not find statistically significant associations between cataract, AMD, or glaucoma—independent of visual acuity—and cognitive dysfunction. Only moderate to severe diabetic retinopathy was independently associated with dysfunction after controlling for concurrent age-related eye diseases.


Ophthalmology summaries are written by Lori Baker Schena, EdD. American Journal of Ophthalmology summaries are edited by Thomas J. Liesegang, MD. Archives of Ophthalmology summaries are written by the lead authors.


Roundup of Other Journals

RNFL Thickness in Children Born Prematurely vs. at Term
British Journal of Ophthalmology

Published online May 8, 2012

Åkerblom et al. found that retinal nerve fiber layer (RNFL) thickness is reduced in children born prematurely with severe or treated ROP (stages 3 and 4) compared with those born at term.

They did not see this RNFL reduction in children who had been born prematurely but had no ROP or had mild ROP (stages 1 and 2). In children born prematurely, reduction in RNFL thickness was associated with low birth weight, but there was no correlation with gestational age at birth. In addition, RNFL thickness did not correlate with visual acuity.

The investigators used optical coherence tomography (OCT) to investigate RNFL thickness in two groups: 62 preterm children born at a gestational age of less than 32 weeks (average age at OCT exam, 8.6 years) and a control group of 54 children with normal birth weight born at term (average age at OCT exam, 10.1 years).

The authors hypothesized that the severe retinopathy may have had an effect on the axons of the ganglion cells, consequently reducing RNFL thickness.


Vision Improves Following Photoreceptor Transplantation


In prior studies, researchers have shown that transplanted rod precursor cells can migrate into the retina and differentiate to develop the features of mature photoreceptor cells. Questions remained as to whether photoreceptor cell transplantation could actually lead to improved vision.

In this study in a mouse model, Pearson et al. demonstrated for the first time that transplanted rod photoreceptor precursors could integrate into a dysfunctional adult retina and improve vision by directly connecting with the host retinal circuitry. The authors found that the transplanted rod precursors were able to form triad synaptic connections with second-order bipolar and horizontal cells in the recipient retina. These cells were responsive to light with dim-flash kinetics.

Not only did the visual signals created by the transplanted rods project to higher visual areas, but the cells could also drive optokinetic head tracking and visually guided behavior under scotopic conditions.


Wireless Photovoltaic Retinal Prosthesis to Restore Useful Vision
Nature Photonics


The majority of retinal prostheses involve coil-decoder and cable-array systems that deliver energy to stimulating electrodes via intraocular cables and require complicated surgical implantation approaches.

However, Mathieson et al. have created a simplified wireless photovoltaic retinal prosthesis in which video goggles deliver both power and visual information directly to each pixel through pulsed near-infrared illumination. This approach would thus eliminate the need for complicated electronics and wiring.

They were able to demonstrate the feasibility of this design by successfully generating in vitro stimulation of healthy and deteriorated rat retina with near-infrared light intensities at least two orders of magnitude below the ocular safety limit. The authors were then able to modulate the response by either pulse duration or irradiance in each pixel.


Roundup of Other Journals is written by Lori Baker Schena, EdD, and edited by Deepak P. Edward, MD.


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