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November/December 2008

 
Journal Highlights
New Findings from Ophthalmology, AJO and Archives
 
 

November’s Ophthalmology:

November’s American Journal of Ophthalmology:

September’s Archives of Ophthalmology:

Roundup of Other Journals:

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Ophthalmology

IOP-Reducing Treatment and Disc Hemorrhages
November’s Ophthalmology

Despite a clear association between disc hemorrhages and glaucoma progression, Bengtsson et al. were unable to demonstrate any effect of IOP-reducing treatment on the presence or frequency of disc hemorrhages in patients who were part of the Early Manifest Glaucoma Trial.

The investigators followed 129 newly detected glaucoma patients treated with argon laser trabeculoplasty plus betaxolol, and 126 newly detected glaucoma patients with no initial treatment. Over 11 years, disc hemorrhages—identified in approximately 55 percent of all patients—were equally common among treated and control patients.

In treated patients, there was no relationship between disc hemorrhages and the extent of IOP decrease. Instead, findings suggested that disc hemorrhages were related to the level of IOP at follow-up rather than to the amount of IOP reduction.

The authors conclude that disc hemorrhages do not necessarily indicate that a patient is receiving inappropriate IOP-lowering treatment. In addition, glaucoma progression cannot be totally halted by IOP reduction in eyes with disc hemorrhages.


Calcium Antagonist Nilvadipine and Glaucoma
November’s Ophthalmology

Nilvadipine is a dihydrophyridine calcium antagonist registered in Japan as a systemic hypotensive drug. Research has shown that this calcium antagonist may have some advantages as a potential vasodilator in ocular neural tissues.

Focusing on patients with low-normal IOP, Koseki et al. conducted a randomized study looking at the effects of oral nilvadipine on visual field performance and ocular circulation in open-angle glaucoma.

Of the 33 patients enrolled, 17 received nilvadipine (2 mg, twice daily) and 16 received placebo. Thirteen patients in each group finished the study. During the three-year study period, IOP averaged 12.6 mmHg in the nilvadipine group and 12.8 mmHg in the placebo group. The nilvadipine group experienced a slightly slower progression in visual field defects and maintained the optic disc rim. In addition, the posterior choroidal circulation increased in these patients. No serious systemic side effects were associated with the calcium antagonist.

The authors conclude that nilvadipine may be a relatively safe ophthalmic calcium antagonist in open-angle glaucoma patients with low-normal IOP.


AMD Genetic Variant Harbored Within HTRA1
November’s Ophthalmology

Findings from multiple samples of age-related macular degeneration cases in the United States and Australia have confirmed that the HTRA1 promoter polymorphism is a global genetic marker for AMD in Caucasian populations.

In this study, Tuo et al. obtained DNA samples from 805 AMD cases and 921 controls from the Eye Clinic of the National Eye Institute, the Age-Related Eye Diseases Study, the Blue Mountain Eye Study Cohort and the Minnesota Lions Eye Bank. Strong associations of the HTRA1 risk allele with AMD were present in all sample sets. This association also was noted for central geographic atrophy and neovascular AMD. The combination of the HTRA1 and complement factor H risk alleles increased AMD susceptibility as did the combination of the HTRA1 risk allele and smoking.

The authors of the study conclude that the risk of advanced AMD increases with the presence of risk factors from HTRA1 combined with either complement factor H risk alleles or a history of smoking.


Near and Distance Activities After Amblyopia Patching
November’s Ophthalmology

In a randomized clinical trial involving 425 children between the ages of 3 and 7 with amblyopia, the Pediatric Eye Disease Investigator Group found no difference in visual acuity improvement between children who performed common near activities and those who performed distance activities during patching treatment.

The children, whose acuity ranged from 20/40 to 20/400, were randomized to two hours of patching per day with near activities or with distance activities. At eight weeks, improvement in amblyopic eye visual acuity averaged 2.6 lines in the distance activities group and 2.5 lines in the near activities group—and remained statistically similar at the 17-week visits, including for those children with severe amblyopia. A look at children with severe amblyopia (20/100 to 20/400) yielded similar results: Children showed improvement in visual acuity with two hours per day of prescribed patching regardless of near or distance activities.


Corneal Disease in Acanthamoeba Keratitis
November’s Ophthalmology

Tu et al. have found that advanced stage of corneal disease at presentation in patients with Acanthamoeba keratitis is highly predictive of worse outcomes.

Through a medical records review, investigators collected patient data on clinical characteristics, treatment methods and final visual outcome of 72 eyes of 65 patients with Acanthamoeba keratitis. The main outcome measure was a final visual outcome worse than 20/25. They found that deep stromal involvement and/or presence of a ring infiltrate at presentation was independently associated with worse visual outcome. Unlike previous reports, symptom duration prior to diagnosis was not predictive of final visual outcome.

The researchers conclude that slit-lamp grade of corneal disease or depth of involvement at presentation in Acanthamoeba keratitis patients is strongly associated with final visual outcomes.


American Journal of Ophthalmology

Accommodation After Implantable Collamer Lens
November’s AJO

Kamiya et al. assessed the time course of accommodative function after implantable collamer lens (ICL) implantation and investigated the relationship between patient age and accommodation in ICL-implanted eyes.

In a clinical trial, the authors examined 69 eyes of 40 patients undergoing ICL implantation with myopic refractive errors of –3.25 to –22.75 D. The amplitude of accommodation was assessed using an accommodometer before and after surgery.

The accommodation was 6.36 ± 3.94 D before surgery and averaged 4.8 D, 4.98 D, 5.16 D and 5.72 D at one, three, six and 12 months after surgery, respectively. The variance of data was statistically significant. There was also a significant correlation between patient age and accommodation before and one year after ICL implantation.

The accommodation was impaired transiently in the early postoperative periods and then recovered gradually over time, indicating that transient dysfunction of the ciliary muscles by ICL fixation may occur after ICL implantation even if the crystalline lens remained intact. In older patients, the amplitude of accommodation became significantly smaller in both normal eyes and in ICL-implanted eyes.


Corneal Ulcer Diagnosis
November’s AJO

Kim et al. compared polymerase chain reaction (PCR) to microbial culture for the detection and identification of bacterial and fungal pathogens in microbial keratitis.

A total of 108 consecutive corneal ulcers were cultured and analyzed by PCR using pan-bacterial and pan-fungal primers. PCR products were cloned, sequenced and compared with culture results using bioinformatics tools.

Of the 108 samples, 56 were culture-positive (25 for bacteria and 31 for fungi) and 52 were culture-negative. After eliminating false-positive PCR products, the authors found that 94 of the 108 samples were positive by PCR (37 for bacteria and 57 for fungi). Nineteen of 25 bacterial culture-positive samples were positive by PCR, and 29 of 31 samples culture-positive for fungi were positive by PCR. The majority of sequenced PCR products matched the positive culture results.

Of the 52 culture-negative samples, 46 yielded pathogen DNA-PCR products (18 bacterial and 28 fungal). These represented a variety of species, including at least three novel, previously uncultured microbes.

The authors conclude that PCR detects microbial DNA in the majority of bacterial and fungal corneal ulcers, and identifies potentially pathogenic organisms in a high proportion of culture-negative cases. They suggest that PCR may be used as an adjunct to culture to identify potential pathogens in microbial keratitis.


Intravenous Thrombolysis With Tissue Plasminogen Activator
November’s AJO

There have been no consistent recommendations concerning the acute treatment of central retinal artery occlusion. Several experimental and clinical studies have indicated that intravenous thrombolysis aiming at rapid restoration of blood flow during the early hours of CRAO may have a beneficial effect. Hattenbach et al. conducted a case series of 28 patients (28 eyes) with acute CRAO who had BCVA of less than 20/100 at entry and onset of symptoms within 12 hours prior to treatment. The investigators evaluated the visual outcome after thrombolytic treatment with low-dose (50 mg) recombinant tissue plasminogen activator and concomitant intravenous heparinization.

Final visual acuity improved three or more lines in nine eyes, stabilized in 18 eyes and worsened in one eye. Time to treatment of less than 6.5 hours after symptom onset was associated with a better gain of lines. Seven of 17 eyes that received thrombolytic treatment within the first 6.5 hours achieved a final BCVA of greater than 20/50, compared with none in the subgroup of patients with treatment after 6.5 hours.


Implantable Telescope for End-Stage AMD
November’s AJO

Hudson et al. evaluated the long-term safety and BCVA results of telescope prostheses in patients with end-stage age-related macular degeneration. This study is a follow-up of previously reported one-year results, with follow-up visits continuing at 18 and 24 months.

At two years, data from 174 of 188 available patients were analyzed. Overall, 103 of 173 telescope-implanted eyes gained three lines or more of BCVA compared with 18 of 174 fellow control eyes. Mean BCVA improved 3.6 lines and 2.8 lines from baseline in eyes with the 3x and 2.2x magnification models, respectively. Mean endothelial cell density stabilized through two years with 2.4 percent mean cell loss occurring from one to two years. There was no significant change in coefficient of variation or percentage of hexagonal endothelial cells from within six months to two years after surgery. The most common complication was inflammatory deposits.

The long-term results of the telescope prosthesis showed that the substantial BCVA improvement at one year was maintained at two years. Key indicators of corneal health demonstrated no significant change in endothelial cell function or structure.


Archives of Ophthalmology

Bevacizumab for Subfoveal Choroidal Metastasis of Colorectal Carcinoma
September’s Archives

Kuo et al. reported the successful short-term regression of a vision-threatening subfoveal choroidal metastasis and associated dramatic visual improvement in a patient treated with three monthly intravitreal injections of bevacizumab.

Visual acuity, fundus examination and fluorescein angiography were obtained. At presentation, visual acuity was hand motions and fluorescein angiography showed profuse late hyperfluorescence and leakage. Five days after injection, the visual acuity was 20/40. After three injections, the visual acuity was 20/30, the posterior pole was restored to a normal contour and fluorescein angiography showed minimal late hyperfluorescence.

According to the authors, the presumed mechanism was the antiangiogenic and antipermeability effects of bevacizumab on the new tumor vessels. The authors write that not only was intravitreal bevacizumab less invasive and less expensive than the alternatives, but also it preserved both the vision and the eye—an important consideration in patients with advanced metastatic disease.


Topical Ketorolac in Vitreoretinal Surgery
September’s Archives

Kim et al. evaluated the effects of topical 0.4 percent ketorolac on intraoperative mydriasis, pain, inflammation, retinal thickness and visual acuity in eyes undergoing vitreoretinal surgery.

The investigators randomized 109 eyes undergoing routine vitrectomy to topical 0.4 percent ketorolac or a placebo. The study drug was begun three days preoperatively (four times daily) and continued four weeks postoperatively.

They recorded and analyzed intraoperative pupil diameter, postoperative pain and inflammation, one-month retinal thickness, and preoperative and one-month postoperative BCVA. There was no difference in mean pupil diameter between ketorolac and the placebo. However, ketorolac significantly reduced pain and inflammation. Ketorolac also reduced central subfield thickness by 8 percent, but this was not statistically significant. At one month, ketorolac eyes demonstrated greater improvement in vision.

The authors conclude that topical ketorolac was well-tolerated and its use reduced pain and inflammation and improved visual recovery after vitreoretinal surgery.


Dietary Omega-3 Fatty Acids and AMD
September’s Archives

SanGiovanni et al. examined the relationship of dietary omega-3 fatty acid intake with incident-advanced AMD in the Age-Related Eye Disease Study (AREDS) using a prospective design in 2,132 participants at mild-to-moderate risk for progression to advanced AMD.

AREDS participants with bilateral drusen at enrollment were followed for a median of 6.3 years (eight years maximum). Professional graders at a reading center ascertained advanced AMD endpoints (neovascular AMD and central geographic atrophy) from annual fundus photographs taken by certified photographers. Participants reported dietary intake at baseline via a validated food frequency questionnaire.

People reporting the highest intake levels of eicosapentaenoic and docosahexaenoic acids were approximately half as likely to progress from bilateral drusen to central geographic atrophy as their peers reporting the lowest intake levels of these nutrients. This analysis included a consideration of other AMD-related factors such as age, smoking and use of the AREDS formulation.

The authors conclude that dietary lipid intake is one modifiable factor that may influence likelihood of developing sight-threatening forms of AMD. Findings from a project examining these issues at 12-years post-AREDS enrollment are forthcoming.
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Ophthalmology summaries are written by Lori Baker Schena 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.


Roundup of Other Journals

Corneal Hysteresis and Optic Nerve Surface Compliance
Investigative Ophthalmology & Visual Science
2008;49:3262–3268

Wells et al. conducted a study looking at changes in optic disc cup depth in a large group of glaucomatous and nonglaucomatous patients during a transient rise in IOP. The investigators compared measurements of the participants’ central corneal thickness (CCT) and corneal hysteresis (CH). The investigators found that in the glaucomatous patients, CH but not CCT (or other anterior segment parameters) was associated with increased deformation of the optic nerve surface during transient elevations of IOP.

This experimental study involved 38 individuals with glaucoma and 62 people without the condition. Both CH and CCT were lower in the glaucoma group (8.8 mmHg and 532 µm) than in the nonglaucoma group (9.6 mmHg and 551 µm). In addition, no statistically significant differences were found between the two groups in terms of spherical equivalent, cylinder, axial length, optic disc size or ocular pulse amplitude.


Retinal Arteriolar Narrowing in Children
Circulation
2008;118:518–524

Mitchell et al. developed a computer-based method to measure retinal microvascular caliber from retinal photographs. With this technique, they previously demonstrated that narrowed retinal arterioles constitute a marker of future hypertension and cardiovascular risk in adults. In this current study, the investigators tested the hypothesis that low birth weight and other indicators of poor early life growth (such as shorter birth length and smaller head circumference) were associated with narrower retinal arteriolar caliber in 6-year-old children.

To test this hypothesis, they looked at 1,369 6-year-old children and measured retinal arteriolar and venular calibers with digitized retinal photographs. Birth information was obtained from the parents. Results showed that lower birth weight, shorter birth length and smaller head circumference were associated with narrower retinal arteriolar caliber. Specifically, each kilogram decrease in birth weight was associated with a 2.3 µm narrower retinal arteriolar caliber.

The results suggest that poor in utero growth may have an adverse influence on microvascular structure, thus leading to an increased susceptibility to develop hypertension and cardiovascular disease in individuals with low and low-normal birth weight.


Swimming Goggles and Elevated IOP
British Journal of Ophthalmology
2008;92:1218–1221

Research from Morgan et al. suggests that wearing certain swimming goggles can elevate IOP. While there have been case reports linking swimming goggles to migraine, supraorbital neuralgia, eyelid swelling, skin irritation and diplopia, the investigators point out that the association between IOP and goggles had not been explored.

This study was divided into two phases. A pilot study with 13 participants was conducted to examine changes in IOP while wearing five different types of goggles. IOP was measured before goggle wear, two minutes after the goggles were placed on the head and then after goggle removal. The second phase was a validation study involving 20 participants testing the predictive model and looking at IOP changes using another eight goggles.

The researchers found that IOP increased by a mean pressure of 4.5 mmHg throughout the duration of the goggle wear. In addition, a smaller goggle face area was consistently associated with greater IOP elevation. The researchers caution these measurements were not taken while participants were swimming. Nonetheless, they suggested glaucoma patients be warned about the potential risk of raised IOP when wearing small swimming goggles.


Alpha 2-Chimaerin and Duane’s Retraction Syndrome
Science
Published online July 3, 2008

Duane’s retraction syndrome is a congenital eye movement disorder caused by aberrant innervation of the extraocular muscles by axons of brainstem motor neurons. Patients experience restricted abduction and in some cases adduction of their eyes—with retraction of the globe upon attempted adduction. Postmortem studies of sporadic Duane’s retraction syndrome show an absence of the abducens motor neurons and cranial nerve with anomalous innervation of the lateral rectus muscle by a branch of the oculomotor nerve.

Miyake et al. have discovered causative heterozygous missense mutations in CHN1, a gene on chromosome 2q31 that encodes alpha 2-chimaerin, a Rac guanosine triposphatase-activating protein (RacGAP). This signaling protein was previously linked to the pathfinding of corticospinal axons in mice. The researchers hypothesized that overexpressing alpha 2-chimaerin may result in aberrant axon development in vivo. They found that expression of mutant alpha 2-chimaerin constructs in chick embryos resulted in failure of ocular motor axons to innervate their target extraocular muscles.

They conclude that alpha 2-chimaerin plays a critical role in ocular motor axon pathfinding.
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Roundup of Other Journals is written by Lori Baker Schena and edited by Deepak P. Edward, MD.