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April 2004

Journal Highlights

New Findings from Ophthalmology, AJO and Archives

Optical Coherence Tomography Delineates Patterns of Macular Edema in Patients with Uveitis

Anterior Capsule/IOL Relationship Is Not Correlated to Central Posterior Capsule Opacification

Choroidal Melanoma Treatment: 10 Years Later, Patients Retain Good Visual Acuity in Fellow Eye

In Elderly Women, Loss of Visual Acuity Is Linked to More Falls

Publication of Redundant Articles in Scientific Journals

In-the-Bag IOL Dislocation: Causes and Treatment

Statin and Aspirin Therapy Are Associated With Decreased Rates of CNV Among AMD Patients

Dropout Rates for Intent-to-Treat and Per Protocol Analyses

Analgesia Using Orbital Catheter Allows Enucleation Patients to Recover at Home

Central Retinal Vein Occlusionin Patients Aged 55 or Younger

Detecting Diabetic Foveal Edema—Clinical Examination vs. OCT

Primary Epithelial Malignancies of the Lacrimal Gland

Compliance Errors With Federal Rules Put University Faculty in “Personal Peril”

Memantine Treatment in Patients With Alzheimer’s Disease Already Receiving Donepezil


Optical Coherence Tomography Delineates Patterns of Macular Edema in Patients with Uveitis

May’s Ophthalmology

Optical coherence tomography is a noninvasive, noncontact, transpupillary imaging technology that can image retinal structures in vivo. Markomichelakis et al. employed the technology to describe the morphologic characteristics of uveitic macular edema and to investigate the correlation between the test’s tomographic features and visual acuity.

The cross-sectional study involved 84 eyes of 60 patients with a clinical diagnosis of macular edema in at least one eye. Three different patterns of fluid distribution in uveitis patients were identified: diffuse macular edema, cystoid macular edema and retinal detachment. Fluid accumulated mainly in the outer retinal layers.

A multivariate analysis revealed that visual acuity was negatively correlated with increased macular thickness, the presence of CME and retinal detachment.

None of the other parameters studied—including sex, type of uveitis, duration of disease or the presence of an epiretinal membrane—had a significant effect on visual acuity.


Anterior Capsule/IOL Relationship Is Not Correlated to Central Posterior Capsule Opacification
May’s Ophthalmology

When using the AcrySof model MA30BA IOL, Vasavada and Raj found no strong correlation between the degree to which the lens capsule covers the optic and the development of central posterior capsule opacification.

In this trial, 202 patients with senile cataracts who received an AcrySof IOL were prospectively randomized to one of three groups. The anterior capsule and IOL optic relationships were as follows: Group 1 had total anterior capsule cover (360 degrees) of the optic, Group 2 had no anterior capsule cover (360 degrees) of the optic and Group 3 had partial anterior capsule cover (< 360 degrees) of the optic.

At three years, there was no significant difference in the incidence of central PCO development among the three groups, and no patient developed central PCO that required YAG capsulotomy.

The authors suggest that with AcrySof model MA30BA, the size and centricity of the rhexis are not critical for prevention of PCO, implying that the surgeon using this IOL does not necessarily have to achieve total cover of the optic with the lens capsule.

Choroidal Melanoma Treatment: 10 Years Later, Patients Retain Good Visual Acuity in Fellow Eye
May’s Ophthalmology

A 10-year follow-up report of surviving patients enrolled in the Collaborative Ocular Melanoma Study (COMS) randomized trials indicates that patients retain good visual acuity in fellow eyes after treatment with standard enucleation or one of two radiotherapy methods.

Since 1986, the COMS Group has conducted two randomized trials of individuals with choroidal melanoma using standard enucle ation or one of two radiotherapy methods: iodine 125 brachytherapy or pre-enucleation external radiation.

For this study, the researchers examined 1,307 of 2,290 fellow eyes five years after enrollment and 358 eyes at 10 years following enrollment.

They found that almost all surviving patients retained good visual acuity in fellow eyes throughout five years of follow-up—findings that persisted through the 10-year period.

These results, taken together with mortality findings and complications after initial treatment of choroidal melanoma, support the conclusion that neither pre-enucleation radiation nor I125 brachytherapy involves any additional risk to patients nor provides any substantial benefit in comparison with enucleation alone.

In Elderly Women, Loss of Visual Acuity Is Linked to More Falls
May’s Ophthalmology

A study by Coleman et al. has linked a decrease in visual acuity with an increased incidence of falls in women 65 years or older.

The prospective cohort study involved 2,002 elderly community-residing women participating in the Study of Osteoporotic Fractures.

Results indicated that older women who had lost one or more letters of visual acuity during a five-year time period had substantially greater odds of frequent falling during the subsequent 12 months of follow-up than did women who did not lose visual acuity or had an improvement in their visual acuity over the same time period.

In addition, a loss of 10 letters or more of visual acuity was associated with 43 percent greater odds of frequent falls during the subsequent year. The authors conclude that in an effort to prevent falls, older individuals should be referred to eye care providers when there is a loss of visual acuity or if it appears visual acuity can be improved with cataract surgery, new eyeglasses or contact lenses.

Publication of Redundant Articles in Scientific Journals
May’s Ophthalmology

Mojon-Azzi et al. report a disturbing discovery in scientific ophthalmologic journals—redundancy.

The researchers defined the term as “a paper that overlaps substantially with one already published or submitted elsewhere in terms of hypothesis, similar numbers or sample sizes, identical or nearly identical methodology, similar results, at least one author in common and no or little new information made available.”

In a retrospective analysis of 22,433 articles published between 1997 and 2000 in 70 ophthalmic journals indexed by Medline, the investigators identified about 1 percent of articles as redundant, with 32 journals and an estimated 1,092 authors involved. In 5 percent of the cases, the scientific conclusions were modified.

The authors believe that these findings are just the tip of the iceberg. While the restrictive selection process in peer-reviewed journals makes it difficult for editors to detect all redundant publications or, in fact, to protect their journals from them, efforts should be made—across all disciplines—to address the problem.

Ophthalmology previews are written by Lori Baker Schena and edited by John Kerrison, MD.


In-the-Bag IOL Dislocation: Causes and Treatment
American Journal of Ophthalmology

In a multicenter, retrospective study, Gross et al. from the Dislocated In-the-Bag IOL Study Group analyzed the surgical treatment and predisposing factors associated with dislocation of the posterior chamber IOL encased within the capsular bag secondary to dehiscence of the zonules supporting the capsular bag.

Their observational case series involved 25 eyes of 22 patients. Associated conditions included pseudoexfoliation syndrome in 44 percent, uveitis in 16 percent and trauma in 16 percent of eyes. There was no identifiable cause in 24 percent of eyes.

The dislocated in-the-bag PC-IOL was repositioned/exchanged and scleral fixated in 40 percent and replaced with an anterior chamber IOL in 60 percent of eyes.

Although in-the-bag PC-IOL dislocations are an unusual, sometimes bilateral, late complication of cataract surgery, they can be managed by exchange with an AC-IOL or by PC-IOL repositioning or replacement with scleral fixation. The most common associated condition was pseudoexfoliation.

Statin and Aspirin Therapy Are Associated With Decreased Rates of CNV Among AMD Patients
American Journal of Ophthalmology

Wilson et al. investigated the relationship between statin and aspirin use and the risk of choroidal neovascularization in AMD patients.

This retrospective consecutive case series, collected over a 13-year period, included patients 60 years and older with AMD who had fundus photographs and fluorescein angiograms. The main outcome measure was angiographically evident CNV. Diagnosis was based on review of fundus photographs and fluorescein angiograms in masked fashion; medical records were reviewed for variables predisposing to CNV or statin use.
Among 326 patients with AMD, 104 had CNV, 204 had dry AMD and 18 had geographic atrophy. Of CNV subjects, 21 (20 percent) used statins, compared with 77 (38 percent) of dry AMD subjects without geographic atrophy and six (33 percent) of controls with geographic atrophy (P = 0.01). Aspirin use was also significantly associated with decreased rates of CNV; 62 CNV subjects (60 percent) used aspirin, compared with 154 (75 percent) dry AMD subjects without geographic atrophy or 12 (67 percent) with geographic atrophy (P = 0.04).

Therapy with statins or aspirin seems to be associated with decreased rates of CNV among AMD patients. Prospective and/or randomized trials of statin and aspirin use in AMD patients are warranted.

Dropout Rates for Intent-to-Treat and Per Protocol Analyses
American Journal of Ophthalmology

Stewart et al. studied the dropout rates for the intent-to-treat and per protocol analyses from prospective, randomized, parallel glaucoma pharmaceutical trials in the literature.

The researchers identified 33 articles (70 treatment arms) that fit the criteria for study. No statistical differences were observed among drug classes for either the intent-to-treat (P = 0.075) or per protocol analyses (P = 0.40).

A difference was observed in the percent dropout rate for the intent-to-treat analyses decreasing with the length of the study (P < 0.0001). This finding was not associated with the number of study visits (P = 0.44). However, a statistically greater percent dropout rate was observed for the per protocol analyses increasing with the length of the study (P = 0.034) and number of study visits (P = 0.01).

No statistical differences were observed with increasing sample size of the study for either the intent-to-treat or per protocol analyses (P > 0.05).

The authors advise that known discontinuation rates for per protocol and intent-to-treat analyses may help in planning sample sizes for future clinical trials.

Analgesia Using Orbital Catheter Allows Enucleation Patients to Recover at Home
Archives of Ophthalmology

Enucleation can result in severe postoperative pain, requiring either outpatient oral narcotics or inpatient analgesia.

Merbs et al. performed a retrospective, noncomparative case series chart review of patients undergoing enucleation on an outpatient basis over a three-year period. At the time of surgery, the patients received an indwelling, orbital pain-control catheter.

Fifty-eight of the 67 patients (87 percent) reported using the catheter at home at least once. Ten of 58 patients reported mild discomfort with catheter use, but in no case did the patient discontinue catheter use because of discomfort.

All patients using the catheter reported pain relief lasting from 90 minutes to four hours.

No postop complications associated with catheter placement were observed.

The orbital pain-control catheter allows a caregiver to easily and repeatedly deliver local anesthetic to the operative site following enucleation, resulting in effective postoperative analgesia while the patient recovers at home.

Central Retinal Vein Occlusion in Patients Aged 55 or Younger
Archives of Ophthalmology

An understanding of the natural course of central retinal vein occlusion is important in deciding the utility and timing of therapeutic intervention.

Findings from the Central Vein Occlusion Study (CVOS) suggested that presenting visual acuity was predictive of ultimate visual and anatomic outcome. However, since the majority of patients in the CVOS were older than 60, these findings may not be applicable to younger patients.

Recchia et al. performed a review of 67 consecutive CRVO patients who were no older than 55. They analyzed data from 57 patients with at least six months’ follow-up and a mean follow-up of 29.2 months. In the cohort of 22 patients with initially good vision (20/40 or better), 42 percent retained vision in that range at most recent follow-up, while 36 percent had worsened to the level of 20/200 or worse. In the cohort of 25 patients with intermediate vision at presentation (20/50 to 20/200), 55 percent retained vision in the same range at 12 months, while 40 percent improved to 20/40 or better and 5 percent worsened to 20/400 or worse. In the cohort of 10 patients with initially poor vision (20/400 to hand motion), 30 percent regained at least 3 Snellen lines of vision by 12 months. None of the six patients with presenting visual acuity of counting fingers or worse improved.

In all groups, visual decline was most common within three to six months of CRVO onset. Visual improvement was uncommon after 12 months.

Intraocular neovascularization was diagnosed at one to nine months following CRVO in 10 patients (18 percent) and was unrelated to presenting age, presenting visual acuity, gender or presence of systemic disease.

In summary, younger patients with CRVO have a variable clinical course. Presenting visual acuity does not appear to be predictive of visual or anatomic outcome. As a significant number of patients with good vision at presentation develop legal blindness, therapeutic intervention during periods of visual decline may be considered.

Detecting Diabetic Foveal Edema—Clinical Examination vs. OCT
Archives of Ophthalmology

Brown et al. compared contact lens biomicroscopy with optical coherence tomography for the detection of diabetic foveal edema.

Among a convenient cohort of 95 consecutive patients with diabetes seen at the Wilmer Eye Institute by retina specialists during one month, there was excellent agreement on the absence of foveal edema when OCT thickness was normal (< 200 micrometers) or moderately to severely increased (> 300 µm). However, agreement was poor when OCT foveal thickness was mildly increased (201 to 300 µm).

In summary, agreement between contact lens examination and OCT for the detection of diabetic foveal edema is poor when OCT thickening is mild. This suggests that contact lens biomicroscopy is relatively insensitive for the detection of mild foveal thickening apparent on OCT but quite sensitive for absence of thickening on OCT or moderate to severe thickening on OCT.

American Journal of Ophthalmology summaries are edited by Thomas J. Liesegang, MD. Archives summaries are edited by the lead authors.

Round-Up of Other Journals

Primary Epithelial Malignancies of the Lacrimal Gland
Ophthalmic Plastic and Reconstructive Surgery
2004;20:10–21 and 22–26

Shields et al. provide an update on primary epithelial malignancies of the lacrimal gland. The report emphasizes the more recently recognized neoplasms and current trends in treatment.

The researchers note that increased knowledge about major salivary gland tumors and the use of immunohistopathologic techniques have led to the recognition of new primary malignancies of the lacrimal gland (PEMLG), such as basal cell adenocarcinoma.

While treatment of adenoid cystic carcinoma (the most frequent and best known PEMLG) has traditionally involved orbital exenteration and removal of adjacent orbital bone, combined with irradiation or chemotherapy, newer approaches for advanced cases have included neoadjuvant intracarotid chemotherapy, with the use of cisplatin (Platinol) and doxorubicin (Adriamycin and Doxil), before orbital exenteration, with postexenteration orbital irradiation.

The authors conclude that the diagnosis and management of PEMLG continues to be challenging.

A study by Esmaeli et al. in the same journal echoes this conclusion. The authors evaluated the outcomes of patients with adenoid cystic carcinoma of the lacrimal gland in a retrospective case series of six men and 14 women treated at a single institution between 1952 and 2002.

The various treatment approaches included exenteration with bone removal and radiation therapy, exenteration with radiation therapy, exenteration, exenteration with bone removal, local resection with radiation therapy and local resection without radiation therapy.

At the time of the report, 13 patients (65 percent) had died of the disease. The authors note that it continues to be difficult to make any conclusive recommendations for local therapy, adding that the major challenge in treating adenoid cystic carcinoma is prevention of systemic metastasis.

They suggest that future efforts should be focused on targeted biological therapies prior to the discovery of any obvious metastasis.

Compliance Errors With Federal Rules Put University Faculty in “Personal Peril”
Journal of Neurosurgery

Richard Winn issues a sober warning to faculty who are working at university-based medical/surgical programs.

His article underlines the importance of acquiring a comprehensive understanding of health care regulations to avoid facing “personal peril.”

On Oct. 28, 2002, after an intensive three-year federal investigation of the neurological surgery department at the University of Washington, the author pleaded guilty to one count of obstructing “the communication of information to a criminal investigator,” although the act was “not intended by the defendant to be fraudulent and was instead the product of mistake and confusion as to the meaning and application of the rules and regulations that controlled the submission of claims to the Medicare, Medicaid and Tricare programs.” As part of the plea agreement, Winn was ordered to publish this article.

The bottom line from this experience? University faculty members, regardless of the organization to which they belong, will be identified by the federal government as the individual responsible in health care finance inquiries.

Indeed, universities are not allowed to shield their faculty from these inquiries—especially if the universities and practice plans are also targets of an investigation.

Consequently, to avoid problems, including criminal prosecution, every faculty member should acquire a full understanding of all health care regulations.

Memantine Treatment in Patients With Alzheimer’s Disease Already Receiving Donepezil
The Journal of the American Medical Association

Memantine is a low- to moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist that is being evaluated as a neuroprotective agent for patients with glaucoma.

It is interesting to note that it also is being evaluated for other neurological conditions.

In patients with moderate to severe Alzheimer’s disease who were receiving stable treatment with donepezil (Aricept), memantine (Namenda) resulted in significantly better outcomes than placebo in terms of cognition, activities of daily living, global outcome and behavior.

Tariot et al. randomized 404 patients with moderate to severe Alzheimer’s disease to receive memantine (starting dose 5 milligrams per day, increased to 20 mg/day) or placebo for 24 weeks. In tests that measured cognition and performance of everyday tasks, such as eating and telephone use, changes in total mean scores favored memantine vs. placebo.

The memantine was also found to be well-tolerated.

The authors conclude that these results suggest memantine may prove a viable treatment alternative for those with moderate to severe Alzheimer’s disease.

Round-Up is written by Lori Baker Schena and edited by Jose S. Pulido, MD, MS, MBA.