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July 2012

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

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Comparing Pupillary Ruff Changes With IOP and Cup-to-Disc Ratio
Published May 2, 2012

In this comparative study matching one patient eye to the fellow eye, Ang et al. compared pupillary ruff changes and associated gonioscopy findings with IOP and cup-to-disc ratio (CDR). They found an association between asymmetric intereye pupillary ruff changes and intereye asymmetry in both IOP and CDR in patients with glaucoma.

The study included 103 patients with a mean age of 64 years recruited from a glaucoma clinic population. Patients who had pseudoexfoliation or previous intraocular surgery or were currently taking IOP-lowering medication were excluded. The authors graded pupillary ruff and associated gonioscopy findings from photographs based on the pupillary ruff atrophy grading system. Study parameters included pupillary ruff absence and abnormality, pupil edge pigment, and trabecular meshwork pigment. The authors used Heidelberg Retinal Tomograph II imaging to determine how intereye differences in pupillary ruff correlated with intereye differences in IOP and CDR.

The average amount of abnormal ruff was 9.5 clock hours and of missing ruff was 5 clock hours. The eye with more pupillary ruff loss was 25 percent more likely than the fellow eye to have greater CDR. Intereye IOP asymmetry was significantly associated with asymmetry of both the amount of abnormal ruff and amount of missing ruff. Intereye CDR asymmetry was significantly associated with asymmetry of both the trabecular meshwork pigmentation and the amount of missing ruff.

The clinical significance of these findings remains unclear. The authors are currently conducting a larger study with longer follow-up to help identify whether isolated pupillary ruff atrophy represents a risk factor for glaucoma.


Decrease in Subfoveal Choroidal Thickness After Ranibizumab
Published May 2, 2012

Yamazaki et al. found a decrease in subfoveal choroidal thickness in eyes with age-related macular degeneration that were treated over a 12-month period with intravitreal injections of ranibizumab. The authors suggest that ranibizumab may have a pharmacologic effect on both choroidal neovascularization and the choroid under the neovascular lesion.

In this interventional case series, the authors treated 40 eyes with AMD with 0.5-mg injections of ranibizumab monthly for three months; patients received additional injections as needed over the following nine-month period. Subfoveal choroidal thickness in all 80 eyes was measured by OCT before and after starting the injections.

Results showed that the mean subfoveal choroidal thickness in all 40 eyes decreased from 244 ± 62 µm at baseline to 234 ± 66 µm at one month, 226 ± 68 µm at three months, 229 ± 67 µm at six months, and 226 ± 66 µm at 12 months. The rate of decrease in subfoveal choroidal thickness was 18 µm/year, a rate greater than that reported in normal eyes.

According to the authors, these results suggest that ranibizumab affects the choroidal structure under the neovascular membrane in patients with AMD.


Comparison of Adult Strabismus Surgery Outcomes
Published April 27, 2012

In an effort to better assess outcomes following adult strabismus surgery, Hatt et al. conducted a cohort study comparing the performance of motor, diplopia, and health-related quality-of-life (HRQOL) criteria both separately and in combinations. They found that the highest postoperative success rates were associated with motor outcome criteria alone. Adding diplopia criteria to motor criteria resulted in lower success rates—but provided a more clinically relevant assessment of overall outcome. Finally, when the investigators applied HRQOL criteria, the success rates were lower still, suggesting that HRQOL criteria represent a more difficult threshold for some patients to cross.

The study involved 159 adults undergoing 171 strabismus surgeries. The authors defined success according to the following parameters: for motor criteria, less than 10 prism diopters by simultaneous prism cover test; for diplopia criteria, absence of diplopia or occurrence only rarely in primary distance and reading positions; and for HRQOL criteria, scores exceeding previously reported 95 percent limits of agreement.

The authors concluded that an accessible method of judging success in adult strabismus surgery involves combining motor and diplopia criteria in a way that utilizes a simple, patient-administered method of diplopia assessment. The HRQOL criteria may be better used in cohort studies.


VEGF Trap-Eye Demonstrates BCVA Gains at One Year in DME
Published April 25, 2012

The phase 2 clinical trial DME and VEGF Trap-Eye: Investigation of Clinical Impact (DA VINCI) was designed to compare intravitreal VEGF Trap-Eye, now known as aflibercept (Eylea), with macular laser photocoagulation in diabetic patients with macular edema. At 24 weeks, VEGF Trap-Eye yielded significant gains in visual acuity over laser therapy. Do et al. compared different doses and regimens of VEGF Trap-Eye with standard macular laser treatment and found that these gains were maintained or improved after one year.

At one year, VEGF Trap-Eye resulted in significantly greater increases in mean visual acuity (+9.7 to +13.1 letters of improvement, depending on dose and regimen) compared with laser alone (–1.3 letters of change). The authors note that this maintenance of efficacy is consistent with the tight binding characteristics and pharmacokinetic profile of VEGF Trap-Eye. They also found that the treatment was relatively well tolerated; the most frequent ocular adverse events included conjunctival hemorrhage, eye pain, ocular hyperemia, and increased IOP.

The authors concluded that VEGF Trap-Eye holds potential as a therapeutic option for managing DME.


American Journal of Ophthalmology

As-Needed Ranibizumab Reinjections for Polypoidal Choroidal Vasculopathy
July’s AJO

Hikichi et al. investigated the one-year outcomes of three monthly intravitreal injections of ranibizumab followed by an as-needed reinjection schedule to treat polypoidal choroidal vasculopathy (PCV). The authors found that the monthly injections improved visual acuity and that a reinjection schedule based on need maintained the improvement. Moreover, the polypoidal lesions resolved in 40 percent of eyes within one year, even though abnormal choroidal vessels remained in all eyes.

In this prospective, consecutive case series, 85 eyes of 82 Japanese patients with previously untreated symptomatic PCV received monthly intravitreal injections of ranibizumab for three months followed by an as-needed reinjection schedule. The authors followed 81 of these eyes for one year. A mean of 4.2 injections were administered over this time period. Twenty-three of 81 eyes (28 percent) did not require additional injections, and 32 eyes (40 percent) required only one injection after the three monthly injections. The mean logMAR visual acuity at baseline was 0.59, which improved to 0.37. Thirty eyes (37 percent) had an improvement in visual acuity of 0.3 or more logMAR units, five (6 percent) had a decrease in visual acuity of 0.3 or more logMAR units, and 46 (57 percent) had a change of less than 0.3 logMAR units. Indocyanine green angiography showed that the polypoidal lesions resolved in 21 eyes (26 percent) at three months and in 32 eyes (40 percent) at one year after the first injection, despite the persistence of abnormal choroidal vessels in all eyes.

The authors concluded that further long-term follow-up is needed to ultimately determine the efficacy of ranibizumab therapy for PCV.


Descemet Membrane Endothelial Keratoplasty Combined With Cataract Surgery
July’s AJO

Laaser et al. determined that Descemet membrane endothelial keratoplasty (DMEK) combined with phacoemulsification and IOL implantation can routinely be performed in cases of endothelial dystrophy and cataract. The authors found that the addition of the cataract surgery to DMEK had no adverse effect on endothelial function or graft adhesion and did not increase the likelihood of postoperative complications.

In a retrospective, single-center, consecutive case series, the authors evaluated the functional and morphologic outcome of this triple procedure in patients with endothelial dysfunction and cataract. The authors performed DMEK with simultaneous cataract surgery in 61 consecutive eyes of 56 patients using corneal donor tissue stored in either short-term culture at 4 degrees C or organ culture at 34 degrees C. Main outcome measures included the number of air injections necessary for graft attachment, BCVA, central corneal thickness, endothelial cell density, refractive spherical equivalent, refractive cylinder, and topographic cylinder at one, three, and six months postoperatively.

At six months, BCVA improved from 0.6 logMAR preoperatively to 0.19 logMAR; endothelial cell density of donor corneas decreased from 2,573 cells/mm2 to 1,550 cells/mm2; and CCT decreased from 651 µm to 521 µm. Refractive spherical equivalent was –0.3 D preoperatively and 0.9 at six months. At that same time point, 55 percent of eyes were within 1 D of emmetropia, and 77 percent were within 2 D of emmetropia. Refractive cylinder was –0.9 D preoperatively and –1.5 D at six months, while topographic cylinder was 2.1 D and 1.7 D, respectively.

The authors also measured a significant shift in topographic cylinder toward lower values between three and six months. Optimized spherical results were achieved by selecting IOLs based on a hyperopic shift of –0.75 D.


Scalability and Severity of Keratoconus in Children
July’s AJO

Léoni-Mesplié found that, at diagnosis, keratoconus is often more advanced in children than in adults and that it exhibits faster disease progression.

In this retrospective study, the authors assessed the severity of keratoconus at diagnosis and its scalability over a period of two years in children and adults. In total, 216 patients were studied, comprising 49 patients (23 percent) under 15 years of age and 167 patients (77 percent) over 27 years of age at diagnosis. The authors assessed severity using Krumeich’s classification and scalability using U.S. FDA criteria.

Keratoconus in children was significantly more severe at diagnosis, with 28 percent—versus 8 percent of adults—having stage 4 disease. In addition, ophthalmoscopic signs were more frequent in children (43 percent versus 30 percent). The authors also found that mean values of maximum, average, and minimum keratometry as well as simulated keratometric astigmatism were higher. Keratoconus was not more likely to worsen in children than in adults; however,  if progression did occur, it was faster and more severe in children, with significant differences in the spherical equivalent and maximum and minimum keratometry.

The authors concluded that early disease detection and close monitoring are crucial in young patients.


Impact of Cataract on Vision-Specific Functioning
July’s AJO

Chew et al. determined that bilateral, but not unilateral, cataracts were significantly associated with poorer vision-specific functioning independent of refractive error. They also found that posterior subcapsular cataracts and cataract combinations had the greatest impact on vision-specific daily activities and that different cataract types caused poorer vision-specific functioning at different severity grades.

In this study, the authors examined 3,400 ethnically Indian patients aged 40 years or older living in Singapore. They assessed cataracts on slit-lamp examination and graded them according to the Lens Opacity Classification System (LOCS) III. The authors also determined vision-specific functioning scores using the Visual Function scale and validated these scores using Rasch analysis.

Two hundred sixty-nine (8 percent) and 740 (23 percent) study participants had unilateral or bilateral cataracts, respectively; and 329 (10 percent), 800 (25 percent), and 128 (4 percent) participants had nuclear, cortical, or posterior subcapsular cataracts, respectively.

In multivariate linear regression models, the presence of bilateral rather than unilateral cataract was independently associated with poorer vision-specific functioning, even after adjusting for undercorrected refractive error. Bilateral nuclear, cortical, and posterior subcapsular cataracts also were associated with poorer vision-specific functioning, and they had even greater impact in combination. Significantly poorer vision-specific functioning occurred at LOCS grades 4 (nuclear opalescence), 5 (nuclear color), 3 (cortical), and 1 (posterior subcapsular) or higher.


Archives of Ophthalmology

Risk and Incidence of Retinal Detachment After Phacoemulsification
June’s Archives

Clark et al. examined the risk factors for and long-term incidence of retinal detachment since the introduction of phacoemulsification cataract surgery in Western Australia. Among other findings, the authors determined that the incidence of detachment after surgery has decreased significantly and that younger age and male sex were the most significant risk factors.

The authors used hospital administrative datasets from the Western Australian Data Linkage System to capture the entire cataract surgery cohort from that region.

After analyzing 65,055 phacoemulsification operations performed there between 1989 and 2001, they identified 237 retinal detachments following surgery. The 10-year cumulative incidence of retinal detachment was 0.68 percent. The number of retinal detachments declined by an average of 19 percent for each year after 1989.  The authors confirmed that younger age and male sex were significant risk factors for retinal detachment: Patients younger than 60 had four times the risk, and men had nearly double the risk. Anterior vitrectomy markedly increased the risk of retinal detachment, with a cumulative incidence at five years of 8.31 percent. 

The authors concluded that these findings have important implications for preoperative counseling and postoperative follow-up of cataract surgery patients, particularly younger patients and those who have complicated surgery.


Incidence and Clinical Characteristics of Periocular Infantile Hemangiomas
June’s Archives

In a population-based study, Alniemi et al. reported the incidence, demographics, and clinical findings  of periocular infantile hemangiomas among a cohort of children in Olmsted County, Minn. The authors found that periocular infantile hemangiomas occurred at a rate of 1 in every 1,586 live births and were most prevalent unilaterally on the upper eyelid of Caucasian female patients.

The authors reviewed the medical records of all patients under age 19 who were diagnosed as having periocular infantile hemangiomas over a 40-year period. They identified 43 children as having periocular infantile hemangiomas, yielding an incidence of 5.4 per 100,000 individuals under age 19, or a birth prevalence of 1 in 1,586 live births. Thirty children (70 percent) were female. There was a history of reduced maternal fertility in approximately 1 in 5 children and premature birth in 1 in 8 children. Twenty-six children (61 percent) had other abnormalities, including secondary hemangiomas in nine (21 percent). Forty-one patients (95 percent) had unilateral disease, and 37 hemangiomas (86 percent) were located on the upper eyelid.


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



Acne Medication Linked to Conjunctivitis
Archives of Dermatology
Published online April 19, 2012

In a retrospective cohort study, Neudorfer et al. found that the acne medication isotretinoin was strongly associated with the development of ocular adverse effects, particularly conjunctivitis. They also found that this risk peaks at four months after the first dispensed isotretinoin prescription. Other common ocular side effects identified in the study included hordeolum, chalazion, blepharitis, eye pain, and dry eye.

The study was conducted using the electronic medical database of a large health maintenance organization in Israel. The authors investigated 14,682 adolescents and young adults who were new users of isotretinoin and two age- and sex-matched comparison groups (one including isotretinoin-naive patients with acne and another including acne-free individuals).

In total, 13.8 percent of the isotretinoin group experienced ocular adverse events versus 9.6 percent of the isotretinoin-naive group and 7.1 percent of the acne-free group. During a one-year follow-up period, the isotretinoin group had significantly higher risk for any ocular adverse events compared with the acne-free group. No such increased risk was observed for the isotretinoin-naive group. The isotretinoin group had higher relative risks for inflammatory and structural adverse events.

The authors recommend that physicians prescribe ocular lubricants to isotretinoin patients as a primary preventive measure. In addition, patients should schedule an appointment with an ophthalmologist about four months after they start the prescription so that any adverse events can be detected.


Botulinum Toxin A to Help Prevent Migraine
Journal of the American Medical Association

Jackson et al. suggest that botulinum toxin A is not associated with a decrease in the frequency of episodic migraine, chronic tension-type headaches, or episodic tension-type headaches. And while botulinum toxin A may help patients in prophylaxis of chronic daily headaches and chronic migraine headaches, this benefit is small and may be limited to patients with chronic migraine headaches.

In this meta-analysis, the authors located 315 articles; and, after applying inclusion and exclusion criteria, they selected 27 placebo-controlled randomized trials and four randomized comparisons with other medications. They categorized headaches as episodic (fewer than 15 headaches per month) or chronic (15 or more per month).

The authors found that the number of headaches per month in patients using botulinum toxin A decreased from 19.5 to 17.5 for chronic migraine and from 17.5 to 15.4 for chronic daily headaches. They also reported a strong association of placebo with improvement in headaches over time. Compared with placebo, botulinum toxin A was linked to a greater frequency of blepharoptosis, skin tightness, paresthesias, neck stiffness, muscle weakness, and neck pain.


Low Prevalence of Ocular Structural Disorders and Nystagmus in Preschoolers
Journal of the American Association for Pediatric Ophthalmology and Strabismus

In a study of infants and children aged 6 months to 71 months in Baltimore, Repka et al. found that structural ocular abnormalities and nystagmus combined are present in approximately 2 percent of this population. In addition, visual loss associated with these abnormalities was uncommon.

The data came from the population-based Baltimore Pediatric Eye Disease Survey, involving 2,546 African-American and Caucasian preschool-aged children. The researchers identified 41 children with structural disorders and nine children with nystagmus, for an overall prevalence of 1.96 percent. Eleven children experienced visual loss in at least one eye, which was most commonly a result of posterior segment disease.


Autoantibodies to Lipoprotein-Related Protein 4 in Double-Seronegative Myasthenia Gravis
Archives of Neurology

In an effort to gain insight into the pathological mechanisms of myasthenia gravis (MG), Zhang et al. focused on whether MG patients have serum antibodies to lipoprotein-related protein 4 (LRP4)—a recently identified receptor for agrin that is crucial for neuromuscular junction formation. The authors found that the receptor does in fact constitute another autoantigen in MG patients. They also discovered that anti-LRP4 autoantibodies may be pathogenic through different immunopathogenic processes.

For this study, the authors tested two groups of serum samples for antibodies to LRP4: a control group of healthy individuals and individuals with other neurologic diseases, and a group of MG patients with known status of serum antibodies to the acetylcholine receptor (AChR) and muscle-specific kinase (MuSK). When LRP4 antibodies were present, the researchers tested those serum samples to determine whether the antibodies could inhibit functions of LRP4 at the neuromuscular junction.

Anti-LRP4 antibodies were detected in 11 of 120 patients with MG without detectable anti-AChR or anti-MuSK antibodies (double seronegative). These anti-LRP4 antibodies were also detected in one of 36 patients without anti-AChR antibodies but with anti-MuSK antibodies; however, they were not detected in any of the 61 patients with anti-AChR antibodies. No healthy control subjects and only two of the 76 control patients with neurologic disease had anti-LRP4 antibodies. Serum samples from patients with MG with anti-LRP4 antibodies were able to inhibit the LRP4-agrin interaction and/or alter AChR clustering in muscle cells.


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


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