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September 2006

Journal Highlights

New Findings from Ophthalmology, AJO and Archives
September's Ophthalmology:
• West Nile Virus: Multifocal Choroiditis Most Common Ocular Manifestation
• Intravitreal Triamcinolone Effective in Advanced Diabetic Macular Edema
• Complement Factor H Increases Risk for Atrophic AMD
• Association Between Glaucomatous Visual Fields and Optic Nerve Head

August's American Journal of Ophthalmology:
• Acanthamoeba Keratitis Outbreak in Chicago Area
• Autologous Serum Aids Corneal Healing in Diabetics Undergoing Vitrectomy
• Health Literacy and Adherence to Glaucoma Therapy

 Archives of Ophthalmology:
• Hormone Therapy and AMD: The Women’s Health Initiative Sight Exam
• Fusarium Keratitis Outbreak in San Francisco
• Disease Severity of Familial Glaucoma Compared With Sporadic Glaucoma
• Fusarium Keratitis Associated With Contact Lens Wear
• Lamina Puncture for Central Retinal Vein Occlusion

Roundup of Other Journals:
• Pars Plana Vitrectomy for Uveitic Cystoid Edema
• Epstein-Barr Virus Linked to Multiple Sclerosis
• Oncomodulin in Axon Regeneration in Retinal Ganglion Cells


West Nile Virus: Multifocal Choroiditis Most Common Ocular Manifestation
September’s issue

Chan et al. found that multifocal choroiditis is the most common ocular manifestation associated with West Nile Virus infection (WNVI). This retrospective, observational case study involved 14 eyes of seven patients diagnosed with WNVI-related ocular manifestations.

The majority of patients with multifocal choroiditis presented with multiple small round chorioretinal lesions scattered throughout the posterior and peripheral fundus. Other ocular findings, in descending order of frequency, were retinal hemorrhages, vitritis, chorioretinal linear streaks, perivascular sheathing and vasculitis, narrowed retinal vessels, disc edema, optic atrophy, vascular occlusion and sixth nerve palsy. Seven eyes had diabetic retinopathy, and patients with diabetes and those over age 50 appeared to be more vulnerable to the severe aspects of WNVI, including more serious ocular lesions.

The authors conclude that while multifocal chorioretinitis is the most common ocular manifestation of WNVI, less common ocular lesions such as optic atrophy and occlusive vasculitis may cause more serious visual problems.

Intravitreal Triamcinolone Effective in Advanced Diabetic Macular Edema
September’s issue

A study by Gillies et al. has shown that treatment with intravitreal triamcinolone acetonide (TA), 4 mg, in eyes with advanced diabetic macular edema reduces macular thickening and improves vision for up to two years with repeated treatment.

This trial involved 34 eyes randomized to receive active treatment (TA injected through the pars plana with a 27-gauge needle) and 35 eyes to placebo (subconjunctival injection of saline). Two-year data were available for 87 percent of eyes. The researchers found an improvement of more than 5 letters BCVA in 56 percent of eyes treated with intravitreal TA, compared with 26 percent of placebo eyes. The intravitreal TA-treated eyes developed moderate but manageable steroid-related adverse events such as cataract progression and elevation of intraocular pressure. However, two eyes in the intravitreal TA-treated group required trabeculectomy.

The investigators acknowledge the need to explore whether there is potential for synergy of steroids and such treatments as photocoagulation and anti-VEGF drugs for DME.

Complement Factor H Increases Risk for Atrophic AMD
September’s issue

In previous studies, the complement factor H gene (CFH) has been shown to be a major risk for age-related macular degeneration. Postel et al. conducted a retrospective, case-control study to determine if this same CFH could determine the risk for developing geographic atrophic AMD (GA; grade 4), which is a significant cause of vision loss without effective treatment.

The researchers tested for the rs1081170 single nucleotide polymorphism in a data set of 647 AMD cases and 163 controls. Not only did CFH increase the risk of developing GA (grade 4) but also neovascular (grade 5) and milder (grade 3) disease. Given the common effect of CFH and the inflammatory pathways likely involved, it may be possible to develop better preventive therapies or treatments for GA. The authors also suggest the current classification schemes for AMD may need modification as science obtains a better understanding of the mechanisms that lead to the atrophic and exudative forms of advanced disease.

Association Between Glaucomatous Visual Fields and Optic Nerve Head
September’s issue

The Ocular Hypertension Treatment Study provided a unique opportunity for Keltner et al. to analyze the association of changes at the optic nerve head with visual field changes in ocular hypertension patients.

The research team applied Cox hazard models to 3,232 eyes, which included 81 eyes that reached a study endpoint by developing a glaucomatous visual field and 128 eyes that reached a study endpoint by developing an optic disc change. They found that an abnormality in either the disc or the visual field may occur before the other, and they are less often detected simultaneously.

The authors assert that ophthalmologists should play close attention to equivocal and nonreproducible changes in the disc or visual field because they represent an increased chance of developing primary open-angle glaucoma.


Acanthamoeba Keratitis Outbreak in Chicago Area
American Journal of Ophthalmology
August’s issue

Acanthamoeba keratitis (AK) has presented in an epidemic pattern on prior occasions. Joslin et al. characterized recent cases of AK and analyzed the geographical distribution within the Chicago area.

All AK cases diagnosed at their center over a recent 30-month period were evaluated in a retrospective, population-based cohort study. Patients with keratitis were identified through confocal microscopy, histology and/or positive cultures. Exploratory analyses were performed to evaluate whether AK cases were unequally distributed geographically. County population data were extracted from U.S. census data from the year 2000, and rates were age-standardized to Cook County. Poisson regression analysis was used to estimate the age-standardized rate ratio (RR) between AK cases and county of residence. These current cases were compared with historical cases in a prior time period to determine if the current rate of AK diagnosis was changing.

Forty AK cases were diagnosed in the 30-month period. The average age of patients with AK was 28; 52.5 percent were men, and 95 percent wore contact lenses. Estimated RR measures demonstrated increased rates for all counties relative to Cook and were significant in two specific surrounding counties. Current AK diagnosis rates were significantly higher than historical rates (RR 6.67).

AK cases are increasing in frequency. The increased rates are unevenly distributed in the study area. Further research seems warranted to better understand the increase and unusual geographical distribution.

Autologous Serum Aids Corneal Healing in Diabetics Undergoing Vitrectomy
American Journal of Ophthalmology
August’s issue

Patients with diabetes frequently have problems with the corneal epithelium following many ocular surgeries, especially pars plana vitrectomy. Schutze et al. compared the effect of autologous serum vs. hyaluronic acid for the treatment of epithelial corneal lesions in patients with diabetes who underwent pars plana vitrectomy and epithelial removal for better intraoperative visualization.

A standardized 8-mm diameter corneal abrasion was performed in this prospective, randomized, masked clinical trial. Patients received either hourly application of autologous serum or hyaluronic acid drops. Beside the time necessary for closure of the corneal epithelium, other parameters such as patients’ age, gender, duration of surgery, history of diabetes, and current HbA1c were evaluated.

A total of 23 patients were enrolled; the autologous serum group consisted of 13 patients, and the hyaluronic acid group consisted of 10 patients. Patients’ mean age was 64.8 years; mean duration of diabetes was 19.4 years. As an average, the operation lasted 145 minutes. Mean epithelialization time was 7.1 days in the hyaluronic acid group compared with 4.3 days in the autologous serum group.

Autologous serum appears to lead to a much faster closure of corneal epithelial wounds after abrasion compared with artificial tears.

Health Literacy and Adherence to Glaucoma Therapy
American Journal of Ophthalmology
August’s issue

Noncompliance with glaucoma medication therapy is a major health problem. Muir et al. evaluated the health literacy of subjects with open-angle glaucoma and investigated the hypothesis that low health literacy is associated with poor glaucoma medication adherence.

A total of 197 subjects with open-angle glaucoma participated in this cross-sectional patient survey and concomitant chart review. The survey included basic demographic information such as age, gender, ethnicity and level of education.

A test of health literacy, the Rapid Assessment of Adult Literacy in Medicine, was performed, and information was collected regarding visual field tests and prescribed medication. The subjects’ pharmacies were contacted to ascertain the number of refills requested over the previous six months.

Although 146 subjects (74 percent) reported completing high school, only 94 subjects (48 percent) read at or above a ninth-grade level, and 23 (11.7 percent) read at a level of third grade or below. The mean number of refills requested by a subject in the preceding six months was not predicted by race, gender, age, mean deviation of the visual field or level of education. There was a positive relationship between health literacy and the number of refills obtained.

Interventions specifically targeting low literacy may improve medication adherence.

Hormone Therapy and AMD: The Women’s Health Initiative Sight Exam
Archives of Ophthalmology
July’s issue

Haan et al. conducted a randomized trial of hormone replacement therapy (conjugated equine estrogen, or CEE) and CEE combined with progestin (CEE+P) in relation to AMD.

Women aged 65 and older received fundus photographs for determination of AMD. Participants (n = 4,262) were evaluated an average of five years after randomization to treatment, and 893 cases of AMD were found.

No association was found between early stage AMD and CEE+P compared with placebo or CEE alone compared to placebo. CEE+P was associated with reduced risk of soft drusen after adjustment for covariates and with a reduced risk of neovascular AMD. Neovascular AMD was lower in the treatment arm of the CEE+P trial compared with the placebo arm.

Treatment with CEE alone or CEE+P does not affect early or late stage AMD. Treatment with CEE+P may reduce the risk of soft drusen or neovascular AMD.

Fusarium Keratitis Outbreak in San Francisco
Archives of Ophthalmology
July’s issue

Bernal et al. describe four cases of Fusarium keratitis (FK) in soft contact lens wearers that presented to the University of California, San Francisco, within a five-week span in early 2006. Three of the four patients had used ReNu with MoistureLoc and one had used ReNu MultiPlus contact lens solution. Notably, FK in soft contact lens wearers had been encountered at UCSF in only two instances in the prior 30 years.

In one case in the current series, a delay in diagnosis and empiric therapy with topical and systemic corticosteroids for presumed herpetic keratitis led to corneal perforation and the need for emergent penetrating keratoplasty. Prompt diagnosis and appropriate antifungal therapy in the remaining cases resulted in final visual outcomes of 20/40 or better.

This cluster from San Francisco parallels contemporaneously published cases of contact lens–associated FK in Singapore and Florida, both tropical or subtropical locations in which Fusarium is endemic. Because FK is so rarely seen in the cool, temperate region of San Francisco, this cluster of cases lends strong credence to the notion that a true outbreak of contact lens–associated Fusarium infections occurred in 2005– 2006 worldwide.

This case series also supports the observed association of recent FK cases with the use of ReNu contact lens solution, particularly ReNu with MoistureLoc, which has since been recalled by the manufacturer.

Disease Severity of Familial Glaucoma Compared With Sporadic Glaucoma
Archives of Ophthalmology
July’s issue

Wu et al. used a cross-sectional study to determine whether there is a difference in disease severity between familial and sporadic cases of primary open-angle glaucoma (POAG).

The Glaucoma Inheritance Study in Tasmania (GIST) severity scores of patients with genealogically confirmed familial POAG were compared to those with sporadic or nonfamilial POAG. GIST severity scores provide a combined weighting of glaucoma severity based on findings from both visual field and optic disc analysis, with and without consideration of intraocular pressure.

Of these subjects, 1,012 of 1,700 (59.5 percent) had familial glaucoma. GIST severity scores were significantly skewed toward greater disease severity in the familial group compared with the sporadic group (p < 0.001). Patients with familial POAG were diagnosed at an earlier age and had greater disease severity scores than patients with sporadic POAG.

The authors suggest that this work may have a significant impact on the allocation of finite POAG screening resources. The identification of individuals at risk of more severe POAG is likely to be more cost effective if screening programs are developed with appropriate weighting toward those with a positive family history of the disease.

Fusarium Keratitis Associated With Contact Lens Wear
Archives of Ophthalmology
July’s issue

Alfonso et al. describe the clinical presentation and course of 34 patients who developed keratitis due to Fusarium infection while wearing nontherapeutic soft contact lenses. The most common antimicrobial medications administered prior to Fusarium diagnosis were antibacterials in 31 of 34.

No distinct preponderance of any one brand of either contact lens or solution was identified. The microbiologic cultures found Fusarium oxysporum in 24 cases, Fusarium solani in four cases and Fusarium not identifiable by species in 18 cases. Patients with a delayed onset of treatment had a tendency for prolonged treatment to cure.

The authors conclude that Fusarium has previously been an unusual organism in the etiology of infectious keratitis in the setting of nontherapeutic soft contact lens wear, and a delay in proper diagnosis and intervention may contribute to a more prolonged treatment course. The microbial spectrum of keratitis may be evolving with broader participation of Fusarium species compared with prior reports.

Lamina Puncture for Central Retinal Vein Occlusion
Archives of Ophthalmology
July’s issue

D’Amico et al. performed transvitreal optic disc lamina puncture on 20 patients in a pilot trial of this procedure as a treatment for CRVO. The procedure was previously evaluated in animals in the laboratory, and is designed to create a perivascular space within the optic disc in order to provide for venous dilation or to actually dislodge the presumed intravascular thrombus by massage performed during the procedure.

Twenty patients with poor initial visual acuity (worse than 20/200) underwent the procedure. Twelve patients had nonischemic occlusions while eight had substantial ischemia on presentation, and the average duration of occlusion prior to the procedure was 5.4 months. When the visual results following the procedure were compared with natural history information available in the Central Vein Occlusion Study (CVOS), there was no significant advantage conferred by undergoing lamina puncture. Neovascularization of the iris with and without glaucoma occurred in five eyes, and these complications were concentrated in eyes with substantial preoperative ischemia.

A meta-analysis of published results of radial optic neurotomy (RON), another transvitreal optic disc surgery for CRVO, was performed, and those results also did not display a significant difference from the CVOS historical controls. The authors conclude that transvitreal optic disc surgery for CRVO, by either lamina puncture or RON, is not effective in restoring visual acuity.


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

Pars Plana Vitrectomy for Uveitic Cystoid Edema
British Journal of Ophthalmology
Published online May 24, 2006

Results from the first randomized controlled study to prospectively investigate the role of vitrectomy on uveitic cystoid macular edema suggest that pars plana vitrectomy may have a beneficial effect on visual function of patients with macular edema secondary to chronic uveitis.

In the pilot study by Tranos et al. 12 patients in the surgical group underwent pars plana vitrectomy, and 11 patients received systemic corticosteroid and/or immunosuppressive treatment.

Interestingly, angiographic improvement was seen in only one-third of the patients undergoing surgery, yet the mean visual acuity in this group improved significantly from 1.0 ± 0.62 at baseline to 0.55 ± 0.29 six months following vitrectomy with five eyes (42 percent) achieving 20/40 or better. In contrast, the medical group’s visual acuity improved only marginally, with 14 percent experiencing angiographic improvement.

While the small sample size did not allow the results of this pilot study to reach statistical significance, the researchers conclude that they provide enough justification to conduct a large-scale trial looking at the effect of vitrectomy on uveitic macular edema.

Epstein-Barr Virus Linked to Multiple Sclerosis
Archives of Neurology

DeLorenze et al. have discovered evidence indicating that serum antibody titers to the Epstein-Barr nuclear antigen (EBNA) complex and EBNA-1 in people with multiple sclerosis are increased up to 20 years before the first symptoms of the disease and then remain constant over time.

For this study, the researchers accessed serum samples drawn between 1965 and 1974 from 42 members of the Kaiser Permanente Northern California health plan who subsequently developed MS.

The stored serum samples were used to compare anti-EBV antibodies in the MS patients with the serum of 42 age-matched and sex-matched controls.

They found that geometric mean titers of antibodies to the EBNA complex and EBNA-1 were significantly higher in the MS patients when compared with matched controls.

Oncomodulin in Axon Regeneration in Retinal Ganglion Cells
Nature Neuroscience

Yin et al. sought to discover how activated macrophages stimulate retinal ganglion cells (RGCs) to regenerate axons through the injured optic nerve, enable dorsal root ganglion neurons to regenerate their central branches into the spinal cord, and facilitate functional recovery after spinal cord injury.

They showed that oncomodulin, a small Ca2+-binding protein, is a potent macrophage-derived growth factor for RGCs and other neurons.

For the first time, they demonstrated that oncomodulin is abundantly expressed and secreted by macrophages, that it binds to RGCs with high affinity, and that in the presence of mannose plus elevated cyclic AMP (cAMP), it activates a Ca2+/ calmodulin kinase II-dependent pathway that leads to axon outgrowth greater than that produced by other known polypeptide growth factors.

Immunodepletion of oncomodulin eliminated the axon-promoting effects of macrophages. In addition, in vivo, continuous release of oncomodulin plus a cAMP analog allowed RGCs to regenerate axons into the adult optic nerve.

The researchers conclude that controlling the delivery of oncomodulin to enhance RGC survival, while counteracting inhibitory signals associated with myelin and the glial scar, may ultimately result in meaningful levels of optic nerve regeneration.


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