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November/December 2004

 
Journal Highlights
New Findings from Ophthalmology, AJO and Archives
 
 

December's Ophthalmology:

Baerveldt Glaucoma Implant Is Effective in Primary and Secondary Refractory Childhood Glaucomas

Undercorrected Refractive Error Is a Significant Problem Among Singaporean Chinese Adults

Aponeurotic Ptosis: Small Incision, Minimal Dissection Is Superior to the Traditional Approach

How Does Preop 5-FU and Low-Molecular-Weight Heparin Affect Proliferative Vitreoretinopathy?

December's AJO:

Macular Edema Associated With BRVO: Two Therapies Compared

Rate of Axial Growth Following Congenital Cataract Surgery

Treatment of Chronic Orbital Myositis With Infliximab

November AJO:

Using OCT to Predict the Visual Outcome of Eyes That Have Macular Idiopathic Holes

OHTS: Corneal Thickness and IOP Response to Medication

Position of Myopic Phakic IOLs Evaluated by Scheimpflug Photo

October's Archives:

Effect of Low-Dose Latrunculin B on Anterior Segment Physiologic Features in the Monkey Eye

Axenfeld-Rieger Anomaly—A Novel Mutation in the Forkhead Box C1 (FOXC1) Gene

Visual Field Defects After ICG Is Administered Intravitreously During Macular Hole Surgery

Optical Coherence Tomography Findings in Myopic Traction Maculopathy

Roundup of Other Journals:

Real-Time Imaging of Retinal Ganglion Cell Apoptosis

VA vs. Commercial Managed Care for Diabetes Care

Artificial Ultraviolet Radiation and Ocular Melanoma

Previews

Baerveldt Glaucoma Implant Is Effective in Primary and Secondary Refractory Childhood Glaucomas
December’s Ophthalmology

Budenz et al. have found that the Baerveldt glaucoma drainage implant appears to be an effective treatment for primary and secondary refractory glaucomas in children.

The study involved 62 children with refractory glaucomas who underwent Baerveldt glaucoma implants. The children ranged in age from 6 weeks to 17 years.

They experienced significant pressure lowering, from 35 mmHg preoperatively to 17.6 mmHg after an average follow-up of 24.8 months. Kaplan-Meier survival analysis showed a cumulative success of 85 percent at six months, 80 percent at 12 months and 67 percent at 24 months. Eight percent of patients had retinal detachments during the follow-up. Because none of the retinal detachments occurred within three months of surgery, their relationship to the implant was unclear.

The investigators concluded that these results are encouraging given the fact many children with refractory glaucoma have already failed medical therapy and other surgeries and are left with few other options to control their intraocular pressure.

Undercorrected Refractive Error Is a Significant Problem Among Singaporean Chinese Adults
December’s Ophthalmology

Vision 2020: The Right to Sight initiative of the World Health Organization has named correction of refractive errors in developed and developing countries as a main priority. Saw et al. offer support for this effort, reporting that undercorrected refractive error is a sizable problem among Singaporean Chinese adults.

The authors conducted a cross-sectional, population-based survey of 1,152 Singaporean Chinese aged 40 to 79 years. The adjusted prevalence of undercorrected refractive error was 17.3 percent, with the highest rates found among older adults who had lower educational levels, did not wear spectacles and had cataract.

The authors express particular concern about the finding that older adults were at higher risk of undercorrected refractive error because they are more prone to falls and that low vision has been shown to increase this risk.

The authors call for strategies to improve the process of updating spectacles while providing education about visual symptoms associated with undercorrected refractive error in individuals at risk.

Aponeurotic Ptosis: Small Incision, Minimal Dissection Is Superior to the Traditional Approach
December’s Ophthalmology

Aponeurotic ptosis correction using a small-incision, minimal-dissection technique is superior in providing a normal eyelid contour and requires less time to perform than a traditional dissection, according to Frueh et al.

In a retrospective study, results from a small-incision, minimal-dissection procedure originally conceived by coauthor McDonald were compared with results from the traditional dissection procedure. The newer procedure was performed on 36 patients (49 ptotic eyelids) and the traditional procedure was performed on 36 patients (49 ptotic eyelids) by the same surgeon (Frueh).

Successful correction of eyelid height and the rate of recommended reoperation were similar in both groups. However, the incidence of attaining good eyelid contour was significantly better in the small-incision, minimal-dissection group. The authors attribute this to less anatomical disruption. In addition, the operating time per lid was markedly less for the small-incision group—25.3 minutes, compared with 55.4 minutes for the traditional dissection group.

Given these findings, the authors recommend small incision, minimal dissection as the surgical procedure of choice for correction of aponeurotic ptosis.

How Does Preop 5-FU and Low-Molecular-Weight Heparin Affect Proliferative Vitreoretinopathy?
December’s Ophthalmology

Does the combination of 5-fluorouracil and low-molecular-weight heparin, given as a preoperative infusion, improve the surgical outcome for severe proliferative vitreoretinothy?

A randomized, prospective, placebo-controlled trial by Charteris failed to show a positive effect. The study involved 157 patients undergoing vitreoretinal surgery and silicone oil exchange with or without membrane peeling and/or retinectomy. They were randomly allocated to preoperative infusion with or without 5-fluorouracil (200 micrometers per milliliter) and low-molecular-weight heparin (5 International units per milliliter) in Hartmann’s solution for one hour.

At six months, 84 percent of patients had full retinal reattachment and 94 percent had stable posterior retinal reattachment. There was no significant difference in the success rate of vitreoretinal surgery between the groups, nor were there differences in complication rates. Secondary macular pucker occurred less often in the treatment group.

The authors suggest alternative strategies to address the lack of effectiveness of many of the agents that have shown promise in treating proliferative vitreoretinopathy in preclinical studies.

Macular Edema Associated With BRVO: Two Therapies Compared
American Journal of Ophthalmology
December’s issue

Yamamoto et al. compared the results of vitrectomy with or without arteriovenous crossing sheathotomy for macular edema associated with branch retinal vein occlusion.

In a retrospective interventional study, the researchers investigated 36 eyes with BRVO-associated macular edema. Of these, 20 eyes underwent arteriovenous sheathotomy and 16 eyes underwent posterior vitreous detachment. BCVA, fluorescein angiography and optical coherence tomography to determine foveal thickness were evaluated preoperatively and at 12 months postoperatively.

Statistical analysis revealed that the mean postop BCVAs were significantly better in both groups. Foveal thickness decreased significantly one month after surgery in both groups and continued to decrease up to 12 months. The postop mean BCVA and improvement of BCVA and foveal thickness were not significantly different for the two groups at any postop period. Postop fluorescein angiography showed reperfusion of the occluded vein in 10 eyes in the arteriovenous sheathotomy group and two eyes in the PVD group, and formation of shunt vessels at the arteriovenous crossing site or around the macular region in fellow eyes of both groups.

It appears that both arteriovenous sheathotomy and simple PVD significantly reduced macular edema associated with BRVO. However, there was no significant improvement of macular function following either procedure. Postop improvement of retinal circulation by either reperfusion of the occluded vein or collateral vessel formation was found. This accounted for functional and morphologic improvements. 

In an accompanying editorial, John Thompson concludes that the vitrectomy rather than the arteriovenous decompression improved the visual acuity.

Rate of Axial Growth Following Congenital Cataract Surgery
American Journal of Ophthalmology
December’s issue

Vasavada et al. evaluated the rate of axial growth following congenital cataract surgery in a prospective observational case series.

The rate of axial growth of 158 eyes (79 children < 10 years old) that underwent surgery was correlated to age at surgery, laterality and visual axis obscuration. After measuring axial length at each follow-up, the mean axial length was calculated (adding the axial length of all eyes divided by their total number). The rate of axial growth is the percentage difference between two consecutive mean axial lengths with respect to the previous reading. The follow-up period was almost five years.

The rate of axial growth in children operated at < 1 year (23.5 percent) was significantly higher than in those at < 3 years (4.8 percent) and at < 10 years (4.3 percent). In children operated at < 1 year, the temporal profile of this growth rate was higher in the first two years after surgery. This growth rate was higher in patients with unilateral pseudophakia at < 1 year (25.53 percent) than in age-matched patients with bilateral pseudophakia (18.5 percent). The rate of axial growth was negligible in children with visual axis obscuration in any group.

The authors conclude that the rate of axial growth is higher in children < 1 year and increases until the second year after surgery. Unilateral pseudophakia revealed accelerated growth compared with bilateral pseudophakia. Visual axis obscuration does not influence the rate of axial growth.

In an accompanying editorial, Edward Wilson and Rupal Trivedi discuss the implications of these findings.

Treatment of Chronic Orbital Myositis With Infliximab
American Journal of Ophthalmology
December’s issue

A number of therapies are available for idiopathic orbital inflammation and most have substantial side effects.

Garrity et al. reported results of treatment with a monoclonal antibody (infliximab) directed against tumor necrosis factor in a retrospective study of seven patients with chronic and difficult-to-control idiopathic orbital inflammation (orbital myositis).

All patients were treated with infliximab after the failure of traditional therapy, which included corticosteroids, radiotherapy or anti-inflammatory chemotherapeutic agents.

All seven patients had a favorable response to treatment with infliximab. One patient with Behçet’s disease required supplemental oral corticosteroids. Pain, swelling and need for concomitant corticosteroids were the primary measures of treatment success. Symptoms of comorbid disease in four patients also improved (Crohn’s disease in two, Behçet’s disease in one and psoriasis in one). There were no untoward effects of treatment after a mean follow-up of 15.7 months.

The authors conclude that treatment with infliximab appears to offer another therapeutic option in cases of recalcitrant or recurrent idiopathic orbital inflammation in which conventional treatment fails.

In an accompanying editorial, Peter Rubin and Stephen Foster further discuss the armamentarium available for this disease process.

Reviews

Using OCT to Predict the Visual Outcome of Eyes That Have Macular Idiopathic Holes
American Journal of Ophthalmology
2004;138:709–716

Quantitative evaluation of the preoperative deformation of the macular hole, presumably from vitreoretinal traction, has not previously been done.

Kusuhara et al. investigated whether an index based on hole configuration can be used to predict visual outcome in eyes with idiopathic macular holes. Thirty-two patients (35 eyes) with idiopathic stage 2 or 3 macular hole were enrolled in this prospective interventional case series. The researchers evaluated the BCVA, cross-sectional image of the macular hole by optical coherence tomography, and retinal thickness in the central, inner and outer ring areas as defined by an OCT retinal mapping program. This was done preoperatively and at one, three, six and 12 months postoperatively. The change in retinal thickness of the inner ring area at the six-month postop period was used to evaluate the degree of preoperative retinal deformation. The macular hole index (hole height/base diameter of hole) was calculated and correlated with minimum diameter of hole, base diameter of hole, the postop decrease in macular thickness and the postop BCVA. The postop BCVA was further evaluated in two patient-matched groups.

Retinal thickness values in the inner ring area were decreased at the one-month postoperative period. The macular hole index significantly correlated with the postop decrease in macular thickness in the inner ring area at six months and with the postop BCVA. Postop BCVA in the index > 0.5 group was better than that in the index < 0.5 group.

The macular hole index is a ratio that can be calculated from OCT transverse images of the macular area. The index represents the preop configuration of a macular hole and is a prognostic factor for visual outcome.

OHTS: Corneal Thickness and IOP Response to Medication
American Journal of Ophthalmology
2004;138:717–722

Corneal thickness has been found to be an important consideration in IOP measurements. Brandt et al. from The Ocular Hypertension Treatment Study group studied whether central corneal thickness correlates with measured IOP response to topical ocular hypotensive medication.

In this prospective randomized clinical trial, researchers performed macular Goldmann applanation tonometry to measure IOP and ultrasonic pachymetry to measure central corneal thickness. The following indicators of IOP response to topical ocular hypotensive medication were examined: IOP after an initial four- to six-week one-eyed therapeutic trial of a nonselective beta-blocker (n = 549) or a prostaglandin analog (n = 201); the mean IOP response during 12 to 60 months of follow-up among medication participants (n = 689); the percentage of follow-up visits at which both eyes met the treatment goal; the total number of different medications prescribed to reach treatment goal; and the total number of different medications prescribed multiplied by the number of months each medication was prescribed.

Central corneal thickness was inversely related to the IOP response after the initial one-eyed therapeutic trial and during 12 to 60 months of follow-up. The mean of the central corneal thickness was not correlated with the number of different medications prescribed during follow-up, the total medication-months or the percentage of visits at which IOP target was met.

Individuals with thicker corneas had smaller measured IOP responses to ocular hypotensive medication than those with normal or thin corneas. The authors conclude that measuring the central corneal thickness may be useful in patient management and in interpreting clinical trials of ocular hypotensive medication.

Position of Myopic Phakic IOLs Evaluated by Scheimpflug Photo
American Journal of Ophthalmology
2004;138:723–731

There have been few studies reporting on the long-term results of implantation of phakic IOLs. A specific concern is postop movement of the phakic IOL. Baumeister et al. examined the postop positional stability of angle-supported, iris-fixated and ciliary sulcus–implanted myopic phakic IOLs.

This prospective, nonrandomized clinical study included 46 eyes of 27 patients with high myopia. One of three types of myopic phakic IOLs was implanted in each eye: an anterior chamber angle-supported phakic IOL (NuVita; 10 eyes), anterior chamber iris-fixated phakic IOL (Artisan; 20 eyes) or ciliary sulcus–implanted phakic IOL (ICL; 16 eyes). The distance between the phakic IOL and the crystalline lens and the cornea as well as rotation around the optical axis was evaluated using Scheimpflug photography at one, three to six months and 12 months postop.

The anterior chamber angle-supported and iris-fixated phakic IOLs showed no significant movement in anteroposterior direction. The posterior chamber phakic IOL showed significant movement toward the crystalline lens between postop months three and 12. The median amount of rotation around the optical axis between the three- and 12-month evaluations was 1.9 degrees for the NuVita, 0.6 degrees for the Artisan and 0.9 degrees for the ICL. Four NuVita IOLs rotated more than 10 degrees.

The angle-supported anterior chamber phakic IOLs showed a generally stable position in the eye over 12 months regarding distance to cornea and natural lens, but rotation was observed in four IOLs. The iris-fixated phakic IOL showed the highest overall stability. The posterior chamber phakic IOL was stable in terms of rotation but had a tendency to decrease in distance to the crystalline lens.

IOLs to correct refractive errors implanted in phakic eyes followed for 12 months demonstrate a somewhat stable IOL position overall.

Effect of Low-Dose Latrunculin B on Anterior Segment Physiologic Features in the Monkey Eye
Archives of Ophthalmology
2004;122:1482–1488

Single and multiple low doses of topical latrunculin B were tested in the living normotensive monkey eye for their effects on outflow facility, IOP, corneal thickness and/or miotic and accommodative responses to pilocarpine.

Okka et al. report that latrunculin B decreased IOP in a dose-dependent manner by up to 4.4 mmHg. They also found that outflow facility was increased by 75 percent and central corneal thickness was not changed.

Miotic and accommodative responses to intramuscular pilocarpine were dose-dependently inhibited, with inhibition of miosis being more substantial than that of accommodation.

In summary, these data suggest that multiple treatments with low topical doses of latrunculin B might substantially reduce outflow resistance (presumably by inhibiting cellular contractility and adhesion in the trabecular meshwork) in glaucomatous eyes without adversely affecting the cornea.

Axenfeld-Rieger Anomaly—A Novel Mutation in the Forkhead Box C1 (FOXC1) Gene
Archives of Ophthalmology
2004;122:1527–1533

Clinical characteristics of Axenfeld-Rieger anomaly were documented by history or examination of symptomatic individuals of a four-generation family. 

Mortemousque et al., after obtaining informed consent, collected a blood sample from each of 10 affected and five unaffected family members. DNA was tested for linkage to the IRID1 locus at 6p25, a known locus for ARA/Rieger syndrome. A candidate gene previously mapped at this locus, FOXC1, was screened for mutations in cases and controls.

A direct sequencing of FOXC1 detected a new mutation, T272C, that segregated with the ARA phenotype in this family and was not detected in DNA from family members without ARA.

This mutation, a T ? C transition, is predicted to result in a change of isoleucine to threonine (Ile9lThr) in a highly conserved location within the first helix of the forkhead domain.

In summary, an analysis of clinical characteristics and DNA from the 6p25 region in a four-generation pedigree of autosomal-dominantly inherited Axenfeld-Rieger anomaly involving the anterior chamber of the eye detected a new mutation (Ile9lThr) in the FOXC1 gene.

Visual Field Defects After ICG Is Administered Intravitreously During Macular Hole Surgery
Archives of Ophthalmology
2004;122:1447–1451

Kanda et al. investigated the incidence of visual field defects after macular hole surgery with indocyanine green-assisted internal limiting membrane peeling and the correlation between the use of ICG and the defects.

In a retrospective, interventional case study, all patients using 0.5 percent ICG solution and three-minute exposure to the retina had postoperative visual field defects, specifically nasal defects. None of the patients using 0.25 percent ICG and immediate washout had visual field defects. Ophthalmoscopy revealed mild to moderate optic disc pallor in some patients with postoperative visual field defects. However, the use of ICG did not affect the visual outcome.

In summary, these data indicate that visual field defects can occur after macular hole surgery with ICG-assisted ILM peeling and that the incidence depends on the concentration of the ICG solution and/or the exposure time to the retina.

Optical Coherence Tomography Findings in Myopic Traction Maculopathy
Archives of Ophthalmology
2004;122:1455–1460

Using optical coherence tomography, Panozzo and Mercanti studied a wide sample of a normal highly myopic population (125 eyes of 121 consecutive patients, ranging from –8 to –26 spherical equivalent) to detect incidence and features of epiretinal traction and related macular damage (myopic traction maculopathy). Epiretinal traction was found in 58 of 125 eyes (46.4 percent) and myopic traction maculopathy in 43 eyes (34.4 percent). Macular retinoschisis was the most frequent macular anomaly (25 eyes, 58 percent), followed by retinal thickening, lamellar hole and shallow retinal detachment.

Only about one-third of patients with myopic traction maculopathy reported progressive visual impairment or metamorphopsiae.

In summary, the researchers conclude that myopic traction maculopathy can affect up to one-third of eyes with high myopia, and should be considered as a separate cause of visual loss.

Optical coherence tomography is the best diagnostic tool to detect this condition, particularly at early stages.

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Ophthalmology previews are written by Lori Baker Schena and edited by John Kerrison, MD. American Journal of Ophthalmology reviews are edited by Thomas J. Liesegang, MD. Archives summaries are edited by the lead authors.

Roundup of Other Journals

Real-Time Imaging of Retinal Ganglion Cell Apoptosis
Proceedings of the National Academy of Sciences
2004;101:13352–13356

Apoptosis is an orchestrated form of cell “death by suicide” and is involved in the pathogenesis of several devastating neurodegenerative conditions, including glaucoma and Alzheimer’s and Parkinson’s diseases.

Cordeiro et al. have developed a noninvasive real-time imaging technique to visualize single nerve cell apoptosis in vivo. The technology utilizes the eye’s optical properties, allowing direct observation of retinal ganglion cells undergoing apoptosis by labeling them with an apoptosis marker and visualizing them with a confocal laser-scanning ophthalmoloscope.

The authors explored this technique with three rat models that generated differing patterns of apoptotic retinal ganglion cell death, as well as in a primate model to determine whether the approach could be transferred to humans. With these models, the investigators were able to image changes occurring in retinal ganglion cells undergoing apoptosis over hours, days and months—demonstrating that effects depended on the magnitude of the initial apoptotic inducer.

According to the researchers, this breakthrough has the potential of allowing for the visualization of single nerve cell apoptosis in the retina of individuals with retinal disease, which could, in turn, lead to development of therapeutic strategies to modulate apoptosis. 

VA vs. Commercial Managed Care for Diabetes Care
Annals of Internal Medicine
2004;141:271–281

Kerr et al. have found that diabetes care in the Veterans Affairs health system is superior to the care provided to patients in commercial managed care.

The investigators conducted a cross-sectional patient survey with retrospective review of medical records at five VA medical centers and eight commercial managed care organizations in five matched geographic regions.

The survey involved 8,205 diabetic patients, 1,285 of whom were in the VA system and 6,920 in commercial managed care.

Patients in the VA system had better scores across the board than those in managed care systems, including 93 percent vs. 83 percent for annual hemoglobin A1c, and 91 percent vs. 75 percent for annual eye examinations. The area that was in particular need of improvement in both systems was blood pressure control.

The researchers conclude that, based on these findings, a federally sponsored national health care organization could provide care that is equivalent or better than the care that is being provided by high-performing commercial managed plans.

They note that investments in information technology, care integration, performance monitoring and payment incentives may help to improve treatment outcomes and reduce end-stage diabetes in commercial plans.  

Artificial Ultraviolet Radiation and Ocular Melanoma
Internatioal Journal of Cancer
2004;112:896–900

A study by Vajdic et al. has confirmed what many have suspected—that exposure to sources of intensive ultraviolet radiation (UVR) such as sunbeds and tanning booths can be dangerous to one’s health.

The investigators found “moderately strong evidence” that use of sunlamps increases risk of choroidal and ciliary body melanoma independently of exposure to solar radiation. They also discovered a weaker link between welding equipment and these conditions. The population-based epidemiologic study involved 290 individuals with ocular melanoma and 893 controls aged 18 to 79 in Australia from 1996 to 1998. Telephone interviews were used to determine exposure levels to welding and the use of sunlamps, including sunbeds and tanning booths.

The investigators found that the risk of choroid and ciliary body melanoma in 246 individuals increased significantly with longer duration of sunlamp use before age 21 and after 1980. The risk of melanomas also rose with increasing duration of welding exposure, yet this trend was not significant overall.

The authors conclude that individuals should shield their eyes from artificial UVR exposure to protect against ocular melanoma.

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