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April 2008

Journal Highlights
New Findings from Ophthalmology, AJO and Archives

April’s Ophthalmology:

April’s American Journal of Ophthalmology:

February’s Archives of Ophthalmology:

Roundup of Other Journals:


Multivitamins and the Risk of Age-Related Lens Opacities
April’s Ophthalmology

According to a study by the Clinical Trial of Nutritional Supplements and Age-Related Cataract Study Group, taking a daily multivitamin-mineral supplement has paradoxical effects on the risk of lens events or need for cataract surgery. The treatment is associated with a statistically significant reduction in the development or progression of nuclear opacity and a statistically significant increase in the development or progression of posterior subcapsular opacity.

The randomized, double-masked trial involved 1,020 participants aged 55 to 75 years with early or no cataract. They were randomly assigned to a daily multivitamin-mineral supplement or placebo, and they were followed for an average of nine years. The researchers note that the broad spectrum of vitamins and minerals in the supplement made it difficult to determine which constituents affected the reduction and increase of nuclear and posterior subcapsular opacities, respectively.

Prevalence of Moderate Hyperopia in Children
April’s Ophthalmology

Ip et al. undertook a study to determine the prevalence of moderate hyperopia in a study of Australian children ages 6 and 12.

They found that the prevalence of moderate hyperopia was 13.2 percent among 6-year-old children and 5 percent among 12-year-old children. It was strongly associated with other common eye conditions such as amblyopia and strabismus, as well as self-reported eyestrain symptoms and parent-reported learning difficulties. The researchers also found a statistically significant association between maternal smoking and moderate hyperopia with the 6-year-old children, but this association was borderline in the 12-year-old group. In addition, early gestational age and low birth weight were not statistically significant predictors of moderate hyperopia in childhood.

Combined Effects of Genotypes and Risk Factors in AMD
April’s Ophthalmology

Wang et al. conducted a study of 278 individuals with age-related macular degeneration from the Blue Mountain Eye Study cohort to assess the risk of AMD by the LOC-387715 polymorphism, by smoking and by inflammatory or hemostatic factors.

The researchers could not replicate the previously reported significant interaction between smoking and the LOC387715 polymorphism, but they did detect a combined effect of the two factors on the risk of late AMD. They also found combined effects of the LOC387715 polymorphism with the inflammatory and hemostatic variables, hsCRP, IL-6, ICAM-1 and PAI-1, particularly on the risk of late AMD, but they did not find significant interactions of these risk factors on AMD.

The investigators conclude that if these results are confirmed in future studies, instituting preventive strategies such as modifying health risk behaviors in individuals with AMD-susceptible gene variants could possibly reduce the incidence of AMD.

Dermis-Fat Grafting in Lower Eyelid Malposition Repair
April’s Ophthalmology

Korn et al. report that dermis-fat grafting represents a novel and effective adjunct in lower eyelid malposition repair—restoring normal eyelid function and providing a well-received cosmetic outcome.

In this case series, 11 individuals with symptomatic lower eyelid malposition after blepharoplasty, trauma, craniofacial syndromes or HIV-associated lipodystrophy underwent a surgical procedure that combined midfacial lifting with dermis-fat posterior lamellar spacer grafting. All patients reported improvement in ocular surface symptoms and restoration of normal eyelid positions. The investigators noted several benefits of using autologous dermis fat as a spacer graft, including the ability to supply both posterior lamellae on the dermis face, volume on the fat side, no risk of a transmissible agent and low incidence of tissue rejection.

Future research plans include evaluating long-term surgical correction, monitoring for signs of late dermal keratinization and hair growth, and evidence of graft-fat atrophy. Investigators also plan to compare the efficacy of dermis fat harvested from different sites.

Older Donor Age for Corneal Tissue Found Suitable
April’s Ophthalmology

The Cornea Donor Study Investigator Group compared graft survival during a five-year follow-up of corneal tissue from donors older than 65 with tissue from donors age 65 or younger.

The trial followed 1,090 patients undergoing corneal transplantation for moderate-risk conditions. Results indicated an overall five-year success rate of 86 percent for grafts both from donors 12 to 65 years old and from donors 66 to 75 years old. The investigators also found that, regardless of donor age, endothelial cell loss was substantial during the first five years after transplant, even when the graft had been successful. They plan to follow the same cohort for another five years to determine the ramifications of this decrease in endothelial cell density.

The authors conclude that the donor pool for corneal tissue should be expanded to include 66- to 75-year-olds.

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American Journal of Ophthalmology

Drug Delivery Implant for Uveitis
April’s AJO

Patients with chronic uveitis frequently require prolonged therapy with corticosteroids. Glenn Jaffe studied the effect of a second fluocinolone implant inserted in eyes in which recurrent inflammation developed after the original implant was placed.

In this trial, 17 eyes of 14 patients with noninfectious posterior uveitis were followed for at least nine months. The patients were treated initially with insertion of a fluocinolone implant and subsequently with placement of, or replacement with, a new implant because of recurrent inflammation.

The mean time from original fluocinolone implantation to first uveitis recurrence was 38 months, and the time from first inflammation recurrence to the second implantation was eight months. The average follow-up was 17 months. Inflammation again developed in only one eye during follow-up (three years after the second fluocinolone implant insertion). There was a significant decrease in adjunctive steroid use, and the mean Snellen visual acuity 12 months after the second implant was 20/78, compared with 20/400 at the time of the original fluocinolone implant placement. The average IOP was unchanged after surgery.

The author concludes that the implant will control ocular inflammation for an average of three years after initial insertion with minimal adverse events. Placement of a new implant can maintain the eye in a quiet state and stabilize or improve visual acuity for an extended time. When the implant is depleted of drug, however, inflammation can recur.

Vitreous Penetration of Oral Valacyclovir
April’s AJO

On rare occasion, herpetic viruses can cause devastating retinal infections that require high doses of intravenous antivirals. Huynh et al. investigated the vitreous penetration of acyclovir, the active metabolite of valacyclovir, after oral administration of valacyclovir.

Ten patients scheduled for elective pars plana vitrectomy were given four oral doses of valacyclovir before surgery. Blood and undiluted vitreous samples were obtained during surgery and were subsequently analyzed with high-performance liquid chromatography to determine the concentrations of acyclovir. Ten eyes of 10 subjects ranging in age from 46 to 83 years were included. All patients had normal renal and hepatic function. Mean serum concentration of acyclovir was 4.41 µm/ml, mean vitreous concentration of acyclovir was 1.03 µm/ml and mean vitreous-to-serum concentration ratio of acyclovir was 0.24 µm/ml.

The vitreous concentrations achieved in noninflamed eyes are within the reported inhibitory ranges for most strains of herpes simplex 1, herpes simplex 2 and varicella zoster virus. The study suggests that orally administered valacyclovir may be an alternative to intravenous acyclovir in the treatment of acute retinal necrosis.

Glaucoma Surgery for Patients on Anticoagulation or Antiplatelet Therapy
April’s AJO

The management of a patient on anticoagulation or antiplatelet therapy is a dilemma for surgeons as there are varying risks in both continuing and discontinuing therapy. Law et al. determined the incidence of and risk factors for hemorrhagic complications in patients on anticoagulation or antiplatelet therapy undergoing glaucoma surgery.

In a review of medical records of patients who had glaucoma surgery, patients who used anticoagulation or antiplatelet therapy continuously throughout the perioperative period or discontinued its use prior to surgery were compared with case-matched controls who were not on these therapies.

The 347 patients who were on anticoagulation or antiplatelet therapy prior to glaucoma surgery had a higher rate of hemorrhagic complications than the 347 control patients.

Moreover, patients on anticoagulation therapy had a higher rate of hemorrhagic complications than those on antiplatelet therapy. Patients who continued anticoagulation therapy during glaucoma surgery had the highest rate of hemorrhagic complications when compared with patients who discontinued anticoagulation therapy prior to surgery or patients who used antiplatelet therapy alone. Hemorrhagic complications following glaucoma surgery were more frequently associated with preoperative anticoagulation therapy, arrhythmia and higher pre- and postoperative IOPs.

The authors conclude that chronic anticoagulation or antiplatelet therapies were associated with a statistically significant increase in the rate of hemorrhagic complications and that perioperative anticoagulation therapy and a high preoperative IOP are risk factors for hemorrhagic complications following glaucoma surgery.

Archives of Ophthalmology

Daclizumab for Birdshot Chorioretinopathy
February’s Archives

Foster el al. reviewed the medical records of eight patients with birdshot chorioretinopathy whose disease was refractory to or who were intolerant of traditional immunomodulatory therapy and who therefore received 1-mg/kg doses of daclizumab.

Over a mean follow-up of 25.6 months, seven patients had either stabilization or improvement in visual acuity of both eyes and complete resolution of vitreous inflammation. Six patients had resolution of vasculitis on fluorescein angiography. While four patients were able to discontinue all other medication and remain inflammation-free while receiving only daclizumab, two patients developed adverse effects that led to daclizumab discontinuation.

The authors conclude that daclizumab is effective in stabilizing vision and decreasing inflammation in most patients with otherwise treatment- resistant birdshot chorioretinopathy.

Infectious Disease Risk Factors of Corneal Graft Donors
February’s Archives

Hassan et al. examined the possible risk factors for infection after corneal transplant surgery. The researchers considered 162 cases of postkeratoplasty endophthalmitis reported to the national surveillance registry of the Eye Bank Association of America over a 10-year period. Two controls were matched to each case by the date of corneal grafting.

Microorganisms were recovered from 121 (75 percent) of infected eyes. Prevalent isolates were streptococci, enterococci, staphylococci and yeasts. While corneoscleral rims were not routinely submitted for laboratory testing, 59 (49 percent) of culture-positive endophthalmitis cases had similar microbial species isolated from the patient’s eye and the donor cornea. When comparing cases to controls, the odds ratio for infections associated with hospital donation was 2.84 and the ratio for cancer-related donor death was 2.46, adjusted for recipient age and for death-to-surgery donation.

Similar relative-effect estimates were found after restriction to culture-positive endophthalmitis or to culture-positive endophthalmitis with concordant donor-rim isolates.

The authors conclude that, while infection after corneal transplant surgery is uncommon, microorganisms can occasionally be harbored by the donor eye tissue. Donors who die in a hospital or who die of cancer have an infrequent but relatively increased opportunity for transmitting bacteria or fungi through penetrating keratoplasty.

Racial Differences in Age-Related Macular Degeneration
February’s Archives

Bressler et al. evaluated racial differences in the prevalence of age-related macular degeneration and its fundus manifestations in a population-based sample. One-quarter of the 2,520 individuals studied were African-American. Small drusen at least 64 µm in size and within 3,000 µm of the foveal center were identified in 56 percent of both African-American and Caucasian individuals. But large drusen greater than 125 µm were more common among Caucasians. Drusen at least 250 µm in size, confluent drusen or a larger area occupied by drusen were each more common among Caucasians, who were also three times more likely to have focal hyperpigmentation than African-Americans. Racial differences were most pronounced for features within 1,500 µm of the foveal center.

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.

Is Your Patient in Pain?

Patients with chronic, refractory, neurogenic or idiopathic pain can pose challenges. For an upcoming story on managing such patients, EyeNet would like to hear from ophthalmologists who have pearls to share or issues to pose. We are especially interested in your thoughts on these questions:

  • What are the common causes of intractable pain in your practice?
  • If you are not a pain specialist, do you tend to refer such patients to specialists or manage them yourself?
  • Has cumbersome paperwork or institutional pressure discouraged you from offering schedule II drugs to appropriate patients?

Please send your succinct opinions to Denny Smith at

Roundup of Other Journals

Pediatric Cataract Surgery and Glaucoma Risk
Investigative Ophthalmology and Visual Science
Published online Jan. 25, 2008

Haargaard et al. have found that infants younger than 9 months of age who undergo cataract surgery are at a substantially increased risk of glaucoma compared with older children who undergo the same procedure.

The investigators conducted a chart review of all children in Denmark younger than 17 years of age who underwent cataract surgery between 1977 and 2001. Out of 946 eyes (595 patients) that underwent cataract surgery, 72 eyes (48 patients) subsequently developed glaucoma. Early surgery in infants under 9 months of age was associated with a 7.2-fold increased risk of glaucoma compared with late surgery (9 months of age and older). A decade after cataract surgery, 31.9 percent of children who had undergone surgery before 9 months of age developed glaucoma, compared with only 4.1 percent of those who had undergone late surgery.

The authors conclude that patients who undergo cataract surgery as infants, particularly those under 9 months of age, should be carefully and continuously monitored for glaucoma.

Oxidative Damage-Induced Inflammation and AMD
Nature Medicine
Published online Jan. 27, 2008

Carboxyethylpyrrole is a unique oxidation fragment of docosahexaenoic acid that previously has been found to adduct proteins in drusen from age-related macular degeneration donor eye tissues and in plasma samples from individuals with the condition. Hollyfield et al. investigated how mice that were immunized with mouse-serum albumin adducted with carboxyethylpyrrole developed AMD-like lesions.

These immunized mice developed antibodies to the hapten, fixed complement component-3 in Bruch’s membrane, accumulated drusen below the retinal pigment epithelium and then developed lesions in the retinal pigment epithelium mimicking geographic atrophy. The authors suggest that this response may have occurred because the mice were sensitized to the generation of carboxyethylpyrrole adducts in the outer retina.

The authors conclude that these findings provide a new model for insight into the early changes in the outer retina in AMD, as well as the disease progression in mice with mutations or polymorphisms in complement pathway genes linked to AMD in humans.

Safety of Coaxial Microincision Cataract Surgery
Journal of Cataract and Refractive Surgery

In a study involving 50 eyes of 50 patients, Dosso et al. compared the outcomes of coaxial microincision cataract surgery (MICS) and conventional coaxial cataract surgery. They found that both techniques had comparable results, although ultrasound and surgical time were significantly higher with coaxial MICS.

For this study, one surgeon performed conventional coaxial cataract surgery on 25 eyes and MICS through 1.6-mm incisions in 25 eyes. The investigators did not find significant differences between the techniques in terms of postoperative visual acuity, endothelial cell loss or corneal thickness. However, they did observe that irrigation turbulence and mechanical trauma by the phaco tip were less during coaxial MICS, suggesting less overall intraoperative trauma with the microincision approach.

The authors conclude that coaxial MICS is a safe and effective procedure that offers several benefits including negligible leakage, good anterior-chamber stability and improved visibility during surgery in eyes with small pupils.

Peters Plus Syndrome Linked to Congenital Glycosylation Disorder
The Journal of Biological Chemistry
Published online Jan. 16, 2008

Peters Plus syndrome is an autosomal recessive disorder caused by splice-site and truncating mutations in what was thought to be a 1,3-galactosyltransferase-like gene. Patients experience anterior eye-chamber defects, short stature, developmental delays and cleft lip and/or palate. Hess et al. performed functional tests to analyze the presumed glycosylation defect in Peters Plus syndrome.

Using a sensitive immunopurification-mass spectrometry method, which employs multiple reaction monitoring, the researchers analyzed O-fucosyl glycans, comparing the reporter protein properdin from Peters Plus patients with that from control heterozygous relatives. While properdin from heterozygous relatives and a healthy volunteer carried the Glc-ß1,3-Fuc-O-disaccharide, the researchers could not detect this in properdin from Peters Plus patients, and in fact only found Fuc-O- at all four O-fucosylation sites.

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

ISRS/AAO in Cancún!

Preregister up to April 16 for the International Society of Refractive Surgery of the American Academy of Ophthalmology meeting, May 29 to 31 in Cancún, Mexico ( It is cosponsored by the Asociación Latina de Cirugía de Catarata Refractiva y Segmento Anterior and the Centro Mexicano de Cornea y Cirugía Refractiva.