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June 2006

 
Journal Highlights

New Findings from Ophthalmology, AJO and Archives
 
 

July's Ophthalmology:
• One in 10 Eye Residents Is Challenged by Surgery
• Glaucoma Linked to Increased Cardiovascular Mortality
• Outcomes of Fellow Eyes After Acute Primary Angle Closure
• Triamcinolone and 5-FU Effective for Recurrent Pterygium

June’s American Journal of Ophthalmology:
• Use of Bactec Broth Culture in the Evaluation of Endophthalmitis
• Smoking Associated With Damage to the Lipid Layer of the Ocular Surface
• Corneal Nerve Regeneration and Sensitivity in LASIK and LASEK
• Cost-Effective Treatment of Patients With Ocular Hypertension

May’s
 Archives of Ophthalmology:
• Effect of Moderate IOP Changes on Topographic Measurements
• Macular Grid Photocoagulation After Triamcinolone Acetonide for Diffuse DME
• Effect of Systemic Administration of Statin on Retinal Circulation

Roundup of Other Journals:
• Natalizumab Shown Safe, Effective in Treatment of Relapsing Multiple Sclerosis
• Researchers Image Tissue and Vascular Layers in the Cat Retina With MRI
• Corneal Graft Survival Decreases Steadily From Time of Surgery


Previews

One in 10 Eye Residents Is Challenged by Surgery
Ophthalmology
July’s issue

In an effort to explore the challenge of certifying surgical competency, Binenbaum and Volpe conducted a written survey asking program directors to describe the prevalence, management and career outcomes of ophthalmology residents who struggle with these skills.

Results from 58 program directors representing 2,179 resident graduates indicated that one in 10 are challenged by surgery. The most frequently cited problems were poor hand-eye coordination and poor intraoperative judgment. Most programs took a supportive rather than punitive approach, providing these residents with extra practice-lab time, scheduling cases with the “best” teaching surgeon, and counseling.

Nearly one-third of these residents overcame their difficulties prior to graduation. However, for the majority of the remaining residents, programs were still likely to grant a statement of satisfactory completion of residency for Board eligibility.

The authors conclude that more specific guidelines for a statement of surgical competency are likely necessary to standardize the Board certification process.

Glaucoma Linked to Increased Cardiovascular Mortality
Ophthalmology
July’s issue

Results from the Blue Mountains Eye Study show that individuals with previously diagnosed glaucoma, particularly those who also use topical timolol, experience significantly increased cardiovascular mortality compared with individuals without glaucoma who do not use timolol.

Lee et al. analyzed data from this population-based cohort involving 3,654 persons aged 49 to 97. At baseline, 108 individuals were diagnosed with glaucoma. Of 873 deaths over 10 years, the age-standardized, all-cause mortality was 24.3 percent in persons with glaucoma and 23.8 percent in those without glaucoma. However, cardiovascular mortality was 14.6 percent in patients with glaucoma and 8.4 percent in those without glaucoma.

The authors hypothesize that timolol used by glaucoma patients may have had an effect on cardiovascular mortality and recommend further studies be conducted to determine if this hypothesis has merit.

Outcomes of Fellow Eyes After Acute Primary Angle Closure
Ophthalmology
July’s issue

Friedman et al. investigated the long-term visual outcome in the contralateral eyes of 79 Asian patients who had experienced an episode of unilateral acute primary angle closure.

At the time of diagnosis, 2.5 percent of fellow eyes had definite or probable glaucoma. Glaucoma developed in 6.5 percent of patients within a mean follow-up of six years. IOP was controlled without surgery in more than 90 percent of patients during the follow-up period (four to 10 years), with a mean IOP of 15.8 mmHg in patients who had not undergone filtration surgery during follow-up. And, visual acuity was well-preserved, with more than 80 percent experiencing vision of 6/9 or better.

Most contralateral eyes treated with prophylactic laser peripheral iridotomy had good vision, well-maintained IOP and no evidence of glaucoma several years after presentation.

Several patients required filtering surgery.

Cataract surgery was very common, pointing to the need for regular follow-up of these patients.

Triamcinolone and 5-FU Effective for Recurrent Pterygium
Ophthalmology
June’s issue

In a randomized clinical trial, Prabhasawat et al. found that intralesional injections of either 5-fluorouracil (5-FU) or triamcinolone were more effective in preventing recurrence of pterygia than topical steroid alone.

The researchers randomly stratified 109 eyes with impending recurrent pterygium into three groups: 35 eyes were the control group, 39 eyes received a 5-milligram intralesional injection of 5-FU weekly for two weeks, and 35 eyes received one 20-mg intralesional injection of triamcinolone. All groups received 1 percent prednisolone acetate eye drops four times daily for eight weeks. They were followed for an average of 10.9 months. Intralesional injection of 5-FU or triamcinolone improved the success rate and reduced the recurrence rate compared with topical steroid alone, with a statistically significant difference in the 5-FU group.

The authors attribute this finding to the possibility that the 5-FU inhibits fibroblastic activity, thus lowering the recurrence rate. Future studies should help determine optimal intervention times and doses of this treatment alternative.

Reviews

Use of Bactec Broth Culture in the Evaluation of Endophthalmitis
American Journal of Ophthalmology
June’s issue

The current traditional culture method for evaluating possible pathogens in endophthalmitis includes inoculation of vitreous samples into solid culture media for bacteria and fungi. Kratz et al. compared the traditional culture method with the Bactec Peds Plus F broth, commonly used for culturing body fluids in pediatric departments, in 13 consecutive cases in a prospective trial over a 28-month period.

The overall growth rate for the Bactec broth was 28.4 percent higher than the traditional method (P = 0.48). In two cases, one of acute-onset postoperative endophthalmitis due to Streptococcus mitis and one of delayed-onset postoperative endophthalmitis attributable to Candida albicans, there was positive growth only in the Bactec broth.

The authors conclude that the Bactec broth can be used successfully in the examination of clinically suspected endophthalmitis. They note that the method appears to have several advantages in time savings, transportation to the laboratory, and the lack of need to maintain a supply of fresh agar media. This method seems especially suitable for office settings and remote clinics, but also can be used in hospital settings.

Smoking Associated With Damage to the Lipid Layer of the Ocular Surface
American Journal of Ophthalmology
June’s issue

Smoking has many known deleterious effects on the eye; Altinors et al. evaluated the effects of smoking on the ocular surface in a prospective, comparative, interventional case series.

Sixty smokers (33 men, 27 women) and 34 nonsmoker controls (18 men, 16 women) were enrolled into the study. The ocular surface was evaluated by measuring corneal and conjunctival sensitivity, surface staining with fluorescein, tear film breakup time, Schirmer 1 test and conjunctival impression cytology. Dry eye symptoms were scored by a questionnaire. Kinetic analysis of sequential tear interference images obtained by a DR-1 tear lipid layer interferometry was used to investigate the precorneal lipid layer spread.

In the smoker group, the mean breakup time was 5.3 seconds, the average conjunctival sensitivity was 26.2 millimeters and the average central corneal sensitivity was 37.6 mm; these values were all statistically worse than in the nonsmoker group. There was no statistically significant difference in goblet cell densities or in Schirmer 1 test values between smokers and controls. Higher grades of lipid layer changes were observed in smokers by DR-1 interferometry kinetic analysis.

The authors conclude that smoking has deleterious effects on the lipid layer of precorneal tear film.

Corneal Nerve Regeneration and Sensitivity in LASIK and LASEK
American Journal of Ophthalmology
June’s issue

Corneal nerve damage is an unavoidable consequence of most refractive surgeries and may have short and perhaps long-term consequences at least in some patients. Lee et al. compared changes in corneal nerve fibers and keratocyte density by confocal microscopy after LASIK and LASEK in a prospective, nonrandomized comparative clinical trial.

Fifty-six eyes of 28 patients who underwent LASIK and 52 eyes of 26 patients who underwent LASEK were included in the study. Confocal microscopic data of the central cornea, corneal sensitivity, tear film breakup time and Schirmer values were determined at three and six months after LASIK or LASEK treatment.

In the LASIK group, corneal sensitivity was reduced from preoperative levels at six months after surgery; in the LASEK group there was no difference between baseline and six-month postoperative values. The number of subbasal nerve fibers and the keratocytes density were also different in the LASIK and LASEK groups. The regeneration of corneal nerves correlated strongly with the recovery of corneal sensation and keratocyte density in both groups, whereas the tear film breakup time, Schirmer values and epithelial thickness did not correlate with corneal nerve regeneration in either group.

The greater decrease in the number of subbasal nerve fibers in the LASIK group compared with the LASEK group seems to relate to the greater decrease in corneal sensitivity. The pattern of corneal nerve regeneration and the recovery of corneal sensation after LASEK did not differ greatly from that after photorefractive keratectomy in previous studies.

Cost-Effective Treatment of Patients With Ocular Hypertension
American Journal of Ophthalmology
June’s issue

The Ocular Hypertension Treatment Study demonstrated that medical treatment of people with IOP > 24 mmHg reduces the risk of the development of primary open-angle glaucoma by 60 percent. There is no consensus, however, on which people with ocular hypertension would benefit from treatment.

The authors performed a cost-utility analysis with the use of a Markov Model. They modeled a hypothetical cohort of people with IOP > 24 mmHg. Four treatment thresholds were considered:

  1. treat no one;
  2. treat people with a > 5 percent annual risk of the development of POAG;
  3. treat people with a > 2 percent annual risk of the development of POAG;
  4. treat everyone.

The incremental cost-effectiveness ratio was then evaluated.

The incremental cost-effectiveness ratios for treatment of people with ocular hypertension were $3,670 per quality adjusted life-year (QALY) for the second threshold and $42,430/QALY for the third threshold. “Treat everyone” cost more than other options. Assuming a cost-effectiveness threshold of $50,000 to $100,000/QALY, the third threshold would result in the most net health benefit. The decision was sensitive to the incidence of POAG without treatment, treatment effectiveness and the utility loss because of POAG.

The authors conclude that, although the treatment of individual patients is largely dependent on their attitude toward the risk of disease progression and blindness, the treatment of those patients with IOP > 24 mmHg and a > 2 percent annual risk of the development of glaucoma is likely to be cost-effective.

Delay of treatment for all people with ocular hypertension until glaucoma-related symptoms are present appears to be unnecessarily conservative.

Effect of Moderate IOP Changes on Topographic Measurements
Archives of Ophthalmology
May’s issue

Nicolela et al. examined the effects of moderate elevation or decrease of IOP on optic disc topography images obtained with the Heidelberg Retina Tomograph (HRT).

Twenty-three patients with bilateral open-angle glaucoma and medically controlled IOP had baseline HRT images followed by discontinuation of glaucoma medications in one eye for one month, after which medications were resumed. The contralateral eye was kept under medications throughout the study. The authors, therefore, induced IOP elevation in one eye during the wash-out period, followed by reduction of IOP in the same eye after medications were resumed, while the contralateral eye served as control. HRT images were obtained at weeks one and four of the wash-out period and then four weeks after reinitiating medications. Optic disc images were analyzed for change in stereometric parameters as well as in discrete locations using the topographic change analysis program of the HRT. Central corneal thickness was measured in order to be correlated with topographic changes induced by IOP variation.

Despite significant IOP increase and consequent decrease induced in the study eyes (in the order of 5 mmHg), no significant optic disc topographic changes were observed. Central corneal thickness was also not associated with optic disc topographic changes. The authors conclude that HRT images are not affected by IOP fluctuations of the magnitude induced in this study.

Macular Grid Photocoagulation After Triamcinolone Acetonide for Diffuse DME
Archives of Ophthalmology
May’s issue

Kang et al. evaluated the outcomes of macular laser photocoagulation, after the intravitreal injection of 4 milligrams of triamcinolone acetonide (IVTA), for diffuse diabetic macular edema (DME).

Eighty-six eyes of 74 patients with diffuse DME were randomized into two groups.

The laser group eyes (48) were subjected to a macular grid laser photocoagulation three weeks after IVTA.The control group eyes (38) underwent only IVTA. Both groups were compared with regard to the changes in visual acuity and central macular thickness at three weeks, three months and six months after IVTA.

The mean central macular thickness before, three weeks after, and three and six months after IVTA were 538, 250, 295 and 301 micrometers in the laser group, vs. 510, 227, 302 and 437 µm in the control group, respectively. The logMAR visual acuities were not significantly different between the two groups at baseline and at three weeks after IVTA, but were significantly better in the laser group at three (P = 0.02) and six months (P < 0.001).

The authors conclude that the macular laser photocoagulation effectively maintains improved visual acuity after IVTA for diffuse DME and reduces recurrent DME after IVTA.

Effect of Systemic Administration of Statin on Retinal Circulation
Archives of Ophthalmology
May’s issue

Recent studies have suggested that in addition to inhibiting cholesterol synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have so-called pleiotropic effects (i.e., improved endothelium-dependent relaxation) and may reduce cerebrovascular and cardiovascular risk, even in patients with normal cholesterol levels. However, the effect of statins on the retinal circulation remains unknown.

Nagaoka et al. investigated the effect of systemic administration of simvastatin on the retinal circulation in a placebo-controlled, double-masked, clinical trial in 12 healthy men. They used laser Doppler velocimetry to measure vessel diameter and blood velocity and calculated retinal blood flow (RBF). They also measured IOP and the plasma level of nitrite/nitrate (NOx), the stable end products of nitric oxide (NO) metabolism.

There were no significant changes in any retinal circulatory parameters at 90 minutes after administration of simvastatin. Daily administration for seven days significantly increased blood velocity and RBF, but did not significantly change vessel diameter. IOP significantly decreased at both 90 minutes and seven days. Simvastatin also significantly increased the plasma NOx concentration.

The authors conclude that simvastatin increases RBF and reduces IOP, probably through the increase in NO.

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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

Natalizumab Shown Safe, Effective in Treatment of Relapsing Multiple Sclerosis
The New England Journal of Medicine
2006;354:899–910

In the search for alternatives to treat relapsing multiple sclerosis, researchers have hypothesized that the interaction between alpha4 beta1 integrin and its targets is a key component of inflammation of the central nervous system in multiple sclerosis, and that the disruption of these interactions and resultant attenuation of inflammation can benefit patients.

Two-year phase 3 results of the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis study now support this hypothesis.

In the study, 627 patients with relapsing multiple sclerosis were randomly assigned to receive a 300-milligram dose of natalizumab, and 315 received placebo by intravenous infusion every four weeks for more than two years.

Polman et al. measured the rate of clinical relapse at one year and the rate of sustained progression of disability at two years.

Natalizumab significantly reduced the risk of progression of disability and the annualized rate of relapse throughout the two treatment years. This effect was realized early in the study and sustained. An 83 percent reduction in the number of lesions detected by T2-weighted MRI and a 92 percent reduction in the number of lesions detected by gadolinium-enhanced MRI point to the strengths of these results. The researchers conclude that continued assessment of long-term treatment with natalizumab will help determine its safety profile.

Researchers Image Tissue and Vascular Layers in the Cat Retina With MRI
Journal of Magnetic Resonance Imaging
2006;23:465–472

Shen et al. have published the first MRI study to demonstrate unequivocal laminar structures in the cat retina. The researchers were able to observe three distinct tissue and vascular “layers” in the retina using multiple MRI contrast mechanisms.

The inner strip nearest to the vitreous overlapped the ganglion cell layer, bipolar cell layer and embedded retinal vascular layer. The middle strip overlapped the photoreceptor cell layer and the inner and outer segments. The outer strip overlapped the tapetum and choroidal vascular layer. Additionally, the researchers found that the inner strip was slightly thicker than the two other strips, with a total thickness of 358 ± 13 micrometers by MRI and 319 ± 77 μm by histology.

The authors note that while one disadvantage of using MRI for resolving laminar structures in the retina is its limited spatial resolution, this imaging tool does have the ability to measure structural, physiological, metabolic and functional data of the retina in a single setting. MRI also has no depth limitation and thus has the potential to serve as a valuable complementary tool with existing techniques for studying the retina.

Corneal Graft Survival Decreases Steadily From Time of Surgery
Transplantation
2006;81:896–901

Williams et al. report that despite almost a century of clinical experience in corneal transplantation, human corneal allograft survival is no better in either the short or long term than that of many other organ transplants.

The researchers reviewed records of 10,952 full-thickness corneal grafts within a national database of 13,831 with a follow-up extending to almost 18 years. They found that the probability of corneal graft survival was 0.86 at one year, 0.73 at five years, 0.62 at 10 years and 0.55 at 15 years. Additionally, graft survival did not improve during a 15-year time frame. This is in contrast to 15-year solid-organ grafts, which generally show steady improvement in a 15-year period. The observation may be attributed to the improvement in systemic immunosuppression, an approach that only has limited viability in corneal transplantation because of the associated morbidities.

Given these findings, the researchers question how corneal graft survival can be improved. Since innovations such as living-related donation and newer immunosuppressive agents cannot be adapted to corneal transplantation, they call for the development of cornea-specific strategies.

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