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Journal Highlights
New Findings from Ophthalmology, AJO and Archives
 
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August’s Ophthalmology:

July’s American Journal of Ophthalmology:

June’s Archives of Ophthalmology:

Roundup of Other Journals:

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Ophthalmology

Ranibizumab for Macular Edema After BRVO
August’s Ophthalmology

In the Ranibizumab for the Treatment of Macular Edema Following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) study, Brown et al. found that intraocular injections of ranibiz-umab are an effective treatment modality for macular edema after branch retinal vein occlusion (BRVO).

At month 12, treatment with ranibizumab as needed maintained the benefits achieved during the first six monthly injections and was associated with low rates of ocular and nonocular safety events. The authors note that these 12-month findings highlight a key observation: Anti-VEGF therapy does not necessarily alter the underlying pathophysiology of an anatomic blockage in the retinal vein.

They maintain that this blockage may in fact compromise arterial perfusion and lead to persistent hypoxia and VEGF production in the affected retina. This, in turn, can result in recurrent edema and decreased vision in many patients once the VEGF blockage diminishes.

The authors call for future treatment alternatives that primarily address the vein blockage or reduce VEGF production as a strategy to decrease the need for ongoing injection therapy. In the meantime, treatment of macular edema after BRVO will most likely involve frequent intraocular anti-VEGF injections.

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Sustained Fluocinolone Acetonide Implant Effective for DME
August’s Ophthalmology

Pearson et al. have shown that sustained drug delivery of fluocinolone acetonide to the posterior segment by means of an implant is effective in treating eyes with persistent or recurrent diabetic macular edema (DME). They point out that the implant becomes depleted of the drug at 30 months, and close patient follow-up is warranted.

The authors looked at the three-year efficacy and safety results of the 0.59-mg fluocinolone acetonide intravitreal implant. The primary efficacy outcome was the percentage of eyes with an increase in visual acuity of at least 15 letters at six months. Visual acuity improved by at least 15 letters in 16.8 percent of implanted eyes at six months compared with 1.4 percent of the eyes randomized to standard of care. In the implant group, the proportion that achieved this outcome increased to 31.8 percent at two years, declining slightly to 31.1 percent at three years.

In addition, the implant group had a higher proportion of eyes showing no evidence of retinal thickening at the center of the macula and a lower rate of decline in Diabetic Retinopathy Severity Scores.

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IOP Control Measurements as Predictors of Long-Term Visual Field Loss
Ophthalmology
Published online, May 20, 2011

In this longitudinal, randomized clinical trial (CIGTS), Musch et al. looked at what measurements of IOP control were the best predictors of visual field loss following the initiation of treatment in patients with open-angle glaucoma (OAG).

The researchers found that three measures of IOP fluctuation—range of IOP, standard deviation of IOP and maximum IOP—are key in detecting the progression of visual field loss.

They randomly assigned 607 patients with newly diagnosed OAG to initial treatment with medications or trabeculectomy. Patients then underwent exams at six-month intervals. In the medication group, higher values of the three IOP measures above were significantly associated with worse visual field outcomes based on mean deviation during a three- to nine-year period. In the surgery group, no IOP measure was significantly associated with mean deviation over time.

From these findings, the authors recommend monitoring for IOP fluctuation and considering more aggressive treatment to limit it. This could be facilitated by using simple software algorithms that provide clinicians with summary information from accumulated IOP data.

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VEGF Trap-Eye Superior to Laser Photocoagulation in DME
Ophthalmology
Published online, May 5, 2011

As part of the DME and VEGF Trap-Eye: Investigation of Clinical Impact (DA VINCI) Study, Do et al. demonstrated that, over a 24-week period, intravitreal VEGF Trap-Eye produced a statistically significant and clinically relevant improvement in visual acuity when compared with macular laser photocoagulation.

In this multicenter, randomized, double-masked, phase 2 clinical trial, the researchers compared different doses and regimens of intravitreal VEGF Trap-Eye with standard macular laser treatment. VEGF Trap-Eye resulted in significantly better mean visual acuity outcomes (+8.5 to +11.4 letters gained) and greater mean reductions in retinal thickness (–127.3 to –194.5 µm) compared with laser alone. Moreover, the different doses and regimens were all individually superior to laser, resulting in statistically significant increases in visual acuity and reduction in retinal thickness at week 24.

These findings indicate that VEGF inhibition may serve an increasingly important role in the treatment of DME.

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OPHTHALMOLOGY IN PRESS. In order to keep our readers current with the newest research, Journal Highlights now features summaries of in-press Ophthalmology articles in addition to those published in the printed journal. Manuscripts of all articles can be found by visiting www.aao.org/one, choosing “Publications,” and “Ophthalmology.”

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American Journal of Ophthalmology

Femtosecond Laser vs. Mechanical Microkeratome for Hyperopic LASIK
July’s AJO

In a retrospective, nonrandomized, interventional, comparative case series, Gil-Cazorla et al. found that, at three months, hyperopic LASIK yielded better refractive results when performed with femtosecond laser than with a microkeratome. The authors note no significant difference in safety between the two procedures.

The researchers compared two groups of age- and refraction-matched patients undergoing hyperopic correction with LASIK: the procedure was performed with a 60-kHz IntraLase femtosecond laser in one group and with a Moria M2 microkeratome in the other.

A total of 144 eyes were analyzed. Mean preoperative sphere was +3.45 D in the IntraLase group vs. +3.18 D in the M2 group. At three months, results in the IntraLase and M2 groups, respectively, were as follows: mean residual sphere, +0.44 D vs. +0.72 D; UCVA, 0.89 vs. 0.80; BCVA, 0.96 vs. 0.92; safety index, 0.97 vs. 0.98; and efficacy index, 0.89 vs. 0.84.

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Patterns of Damage in Chronic Angle-Closure Glaucoma vs. Primary Open-Angle Glaucoma
July’s AJO

In a cross-sectional study, Nouri-Mahdavi et al. found that patterns of glaucomatous damage seem to be different in chronic angle-closure glaucoma (CACG) than in primary open-angle glaucoma (POAG). If the findings are confirmed in a larger prospective study, they may have significant implications with regard to early detection of the disease and its progression in eyes with CACG.

The researchers enrolled 32 patients (32 eyes) with CACG. Patient selection was based on the availability of good-quality Heidelberg Retina Tomograph (HRT) images and stereoscopic disc photographs taken within one year of visual field assessment that showed reproducible glaucomatous field loss. The researchers also selected control eyes with POAG that met similar criteria. They matched the control eyes for severity of field loss and race. The outcome measures included presence of focal rim loss, HRT stereometric parameters and extent and location of field loss.

The average mean deviation was –5.1 dB in both groups. Patients with CACG were more hyperopic and had higher IOP at the time of imaging. Focal disc damage was as frequent in CACG eyes as in those with POAG. Eyes with CACG had smaller cup area, cup volume and cup depth, and larger rim/disc area ratio. These differences persisted after adjusting for disc size, age, refractive error and IOP. The average number of abnormal test locations was similar in the two groups, although CACG eyes were less likely to have paracentral points involved.

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Efficacy of Systemic Cyclosporine in High-Risk Corneal Transplantation
July’s AJO

In a randomized, open-label clinical trial, Shimazaki et al. were unable to detect a positive effect from the use of systemic cyclosporine (CsA) to suppress immunologic rejection in high-risk corneal transplantation. With a relatively high incidence of systemic adverse effects, the results suggest that this protocol might not be recommended for corneal transplantation, especially in elderly patients.

Patients who underwent high-risk corneal transplantation (defined as corneal neovascularization in more than one quadrant or a history of corneal grafting) were assigned to either a systemic CsA group or a control group. Administration of CsA was continued for at least six months unless adverse effects developed. The main outcome measures were graft clarity, endothelial rejection and local or systemic complications.

Forty patients were enrolled and 39 (18 men, 21 women; mean age, 67.4 years) were analyzed. In the CsA group, treatment was discontinued within six months in seven patients because of adverse effects. At mean follow-up of 42.7 months, endothelial rejection had developed in six eyes in the CsA group and two eyes in the control group. Using Kaplan-Meier analysis, the researchers found no differences in the rates of graft clarity loss between the two groups.

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Archives of Ophthalmology

Chemotherapy and Retinoblastoma
June’s Archives

Gobin et al. found that selective intraophthalmic artery chemotherapy is safe and effective for treatment of advanced intraocular retinoblastoma in children.

The study included 78 patients (95 eyes) with unilateral or bilateral retinoblastoma. Catheterization of the ophthalmic artery and selective injection of chemotherapy were performed under general anesthesia in an outpatient setting. Drug dosage was determined by patient age and angioanatomy. The main outcome measure was event-free eye survival (i.e., no enucleation or radiotherapy).

Catheterization was successful in 98.5 percent of procedures, and 289 chemotherapy injections were administered. Kaplan-Meier estimates of event-free eye survival at two years were 70 percent for all eyes, 81.7 percent for eyes that received intraarterial chemotherapy as primary treatment and 58.4 percent for eyes that had previous treatment failure with intravenous chemotherapy and/or radiation. There were no permanent extraocular complications.

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IOP Response and Selective Laser Trabeculoplasty
June’s Archives

Shazly et al. found that the percentage of IOP reduction after selective laser trabeculoplasty (SLT) in the first treated eye was predictive of response to SLT in the fellow eye.

Forty patients (80 eyes) with bilateral ocular hypertension or primary open-angle glaucoma received primary SLT in both eyes three months apart and completed 30 months of follow-up. Analysis was performed to determine correlations between the three-month percentage of IOP reduction after SLT in the first treated eye and long-term percentage of IOP reduction in the fellow eye in response to SLT.

In patients with ocular hypertension, the three-month percentage of IOP reduction in the first treated eye correlated strongly with long-term percentage of IOP reduction in the fellow eye up to 30 months. In patients with primary open-angle glaucoma, the three-month percentage of IOP reduction in the first treated eye correlated moderately with the percentage of IOP reduction in the fellow eye up to nine months.

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Foveal Damage in Habitual Poppers Users
June’s Archives

Although it has been shown that a single dose of the recreational drug known as poppers may cause retinal damage, Audo et al. found no involvement of the retina, apart from the fovea, even after years of poppers use. They note that foveal damage can heal after the drug is stopped, although this may take several months.

The researchers examined six patients who had used poppers regularly for several months or years; isopropyl nitrite was identified in the vials taken by three of them. All of the patients complained of chronic, progressive, moderate bilateral visual loss, and visual acuity ranged from 20/50 to 20/25. Two patients had photopsias, and all patients had alteration of foveal outer segments as revealed on OCT. The foveal damage was best identified by adaptive optics imaging.
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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.

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Roundup of Other Journals

Severe Primary Open-Angle Glaucoma Linked to Increased Vehicle Collisions
Investigative Ophthalmology and Visual Science
Published online March 29, 2011

Tanabel et al. found that patients with severe primary open-angle glaucoma (POAG) and visual field defects corresponding to a mean deviation of –10 dB or worse had higher odds of being involved in motor vehicle collisions (MVCs) than patients with mild or moderate POAG and control patients without glaucoma. The researchers also suggest that the likelihood of being involved in MVCs increases when the degree of visual field defects crosses a certain threshold.

The study involved 121 patients with POAG who were classified into three subgroups of mild, moderate or severe disease, and 144 participants with no ocular disease. All participants related their 10-year driving history via a questionnaire. Study findings showed that 25 percent of the severe POAG group had experienced MVCs compared with 3.5 percent of the controls, none of the mild POAG group and 3.9 percent of the moderate POAG group.

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Impact of Eye Rubbing and Breath Holding on Ocular Exams
Cornea
Published online April 19, 2011

According to a report by Liu et al., eye rubbing significantly decreases measurements of the cornea’s biomechanical properties and Goldmann-equivalent IOP (IOPg). But it does not significantly affect corneal-compensated IOP (IOPcc). On the other hand, breath holding—which patients may do while being examined in the clinical setting—does not significantly affect any of these measurements and need not be a concern to the clinician during eye exams.

The researchers conducted the study based on the observation that patients may rub their eyes—consciously or unconsciously—before ocular examinations as well as hold their breath during examination because of nervousness or unfamiliarity with procedures.

To determine the impact of these behaviors, the researchers measured corneal hysteresis, corneal resistance factor, IOPcc and IOPg in both eyes of 40 patients. Baseline measurements were taken before eye rubbing and breath holding, immediately after two episodes of eye rubbing (in which patients were asked to rub their eyes in the same manner and with the same force each time) and during two episodes of breath holding.

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RNA’s Role in the Development of Cataract
Science
2011;331(6042):1523–1524, 1571–1576

The study of genetic factors in the development of cataracts has traditionally centered on mutations in genes that encode the structural proteins of the lens. This includes mutations in genes encoding transcription factors (such as cMaf, Hsf4 and Pitx3) that regulate the expression of these structural genes.

However, Lachke et al. focused on RNA in the lens, suggesting that RNA-containing granules could regulate both the subcellular localization and processing of lens mRNAs involved with lens transparency.

They identified two independently occurring mutations in the human Tutor domain-controlling 7 (TDRD7) gene and one mutation in the mouse gene TDRD7 that result in cataract formation. Many members of the TDRD family, including TDRD7, are found in cytoplasmic RNA granules, which function in the posttranscriptional control of gene expression.

According to an accompanying editorial by Melinda K. Duncan, this research runs counter to long-standing beliefs that lens gene expression is largely controlled at the transcription level; Lachke et al. showed that the vertebrate lens contains several classes of RNA granules and that TDRD7-containing granules play a key role in normal lens function.

Dr. Duncan notes that these findings open up a new field of investigation studying both the physiological and biochemical functions of RNA granules in the lens.

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Self-Organizing Optic-Cup Morphogenesis
Nature
2011;472(7341):51–56

Using a simple 3-D embryonic stem cell culture system, Eiraku et al. demonstrated how collective cell behavior emerges in a nonequilibrium biological process that occurs spatiotemporally. Specifically, the researchers showed the dynamic, autonomous formation of the optic-cup structure from a 3-D culture of mouse embryonic stem cell aggregates. They found that processes such as optic-cup morphogenesis depend on an intrinsic self-organizing program that involves specific steps and domain-specific regulation of local epithelial properties.

In this study, retinal epithelium derived from embryonic stem cells spontaneously formed hemispherical epithelial vesicles that became patterned along their proximal-distal axis. The proximal portion differentiated into mechanically rigid pigment epithelium. Meanwhile, the flexible distal portion progressively folded inward to form a shape resembling an embryonic optic cup; this same distal portion reflected interkinetic nuclear migration and generated stratified neural retinal tissue.
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Roundup of Other Journals is written by Lori Baker Schena, EdD, and edited by Deepak P. Edward, MD.

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CALLING ALL EDITORS!

The Academy is conducting a search for a new editor-in-chief of its journal Ophthalmology, as Andrew P. Schachat, MD, comes to the end of his term on Dec. 31, 2012, after a successful 10 years in the hot seat. The successful applicant will be able to recognize important contributions to the literature and mobilize the editorial board and reviewers to aid in peer review. The applicant will also continue the successful rise in the impact factor ranking, which now stands at 5.491.

Given the ease of online management currently experienced by the journal, we plan to keep the editorial office in Baltimore under managing editor, Veronica Doyle.

Please send application and CV to Ryan Plumb at rplumb@aao.org



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