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May 2004

Journal Highlights

New Findings from Ophthalmology, AJO and Archives

Prevalence of Age-Related Maculopathy Among Seniors

MMC and Ahmed Glaucoma Valve Implantation

Calculating Retinoblastoma Rates

Autologous Serum Application for Neurotrophic Keratopathy

Is Radiation Required in the Treatment of Conjunctival Malignant Lymphoma?

Diffuse Structural Damage in Glaucomatous Eyes With Localized Visual Field Abnormalities

Multifocal Electroretinogram Reveals Transient Reduction in Retinal Function After PDT

The Short-Term Visual Effects of Viagra in Healthy Young Men

Using the Artificial Silicon Retina Chip for the Treatment of Vision Loss Due to Retinitis Pigmentosa

The Prevalence of Refractive Errors Among Adults in the United States, Western Europe and Australia

Management of Ocular Surface and Tear Film in LASIK

Radiotherapy for Recurrent CNV Complicating AMD

Pediatric Trends: The Increasing Incidence of Paintball Injuries

Supplemental Oxygen Improves Diabetic Macular Edema


Prevalence of Age-Related Maculopathy Among Seniors

June’s Ophthalmology

Findings from The Visual Impairment Project, a population-based cohort study in the state of Victoria in Australia, indicate that one in three people aged 70 or older will experience age-related maculopathy lesions over a five-year period and that the disease is likely to progress to a more severe form after 80 years of age.

Mukesh et al. recruited 3,271 participants aged 40 and older. They conducted baseline examinations in the early 1990s and follow-ups five years later.

The overall cumulative five-year incidence of macular degeneration was 0.49 percent and that of early ARM was 17.3 percent. Individuals with soft, indistinct drusen with pigmentary abnormalities had a 9.5-time higher risk of developing AMD compared with people with soft drusen or pigmentary abnormalities.

Those with unilateral early ARM at baseline were three times as likely to have early ARM in their second eye when compared with people with no ARM in both eyes.

Given these statistics, the researchers call for preventive strategies to reduce visual disability from AMD. 

MMC and Ahmed Glaucoma Valve Implantation
June’s Ophthalmology

Costa et al. found that adjunctive intraoperative mitomycin C does not increase the success rate after Ahmed glaucoma valve implantation.

In this study, the first prospective randomized trial looking at the use of intraoperative MMC during the implantation of a glaucoma aqueous shunt, 60 eyes of 60 patients received either intraoperative MMC (0.5 milligrams per milliliter for five minutes) or balanced salt solution.

Using a postoperative IOP between 6 and 21 mmHg as a criterion of success, results of Kaplan-Meier survival analysis indicated 59 percent probability of success at 18 months for the MMC group and 61 percent for the control group.

When an IOP reduction of at least 30 percent was used as the criterion for success, the authors found a probability of success at 18 months of 62 percent for the MMC group and 67 percent for the control group. Additionally, there were no differences between the incidences of postoperative complications in both groups.

Calculating Retinoblastoma Rates
June’s Ophthalmology

Traditionally, the incidence of retinoblastoma was calculated by tracking live births in a given year. However, some question the accuracy of this method because retinoblastoma is seldom diagnosed in newborns, and live-born children do not represent the number of children at risk of retinoblastoma in a given year.

In a retrospective cohort study, Seregard et al. also found problems calculating incidence by tracking live births. Using data of 291 Swedish and 174 Finnish children diagnosed with retinoblastoma between 1958 and 1998, they calculated incidence both by standard analysis per child less than five years of age and per live births and by birth cohort analysis.

While analysis based on year of diagnosis suggests a moderate increase in incidence since 1990, birth cohort analysis demonstrates stable incidence rates for both countries.

The researchers conclude that birth cohort analysis should be used in future epidemiologic studies of retinoblastoma.

Autologous Serum Application for Neurotrophic Keratopathy
June’s Ophthalmology

Current treatment approaches for epithelial disorders in neurotrophic keratopathy include the use of bandage contact lenses, topical artificial tears, sodium hyaluronate, fibronectin, substance P, insulin-like growth factor and nerve growth factor eye drops.

To explore an alternative modality, Matsumoto et al. evaluated the effect of autologous serum application on 14 eyes of 11 patients with neurotrophic keratopathy in a retrospective, noncomparative case series. These patients received 20 percent topical autologous serum eye drops five to 10 times daily until the neurotrophic keratopathy resolved.

All eyes experienced healing of the epithelial disorders within six to 32 days, with a decrease in corneal scarring. The BCVA improved by more than 2 Landolt lines in 78.6 percent of the eyes. The researchers also discovered that the autologous serum harbored neurotrophic factors such as nerve growth factor, insulin-like growth factor and substance P.

They conclude that autologous serum treatment holds promise for neurotrophic keratopathy patients, providing healing factors to a compromised ocular surface.

Is Radiation Required in the Treatment of Conjunctival Malignant Lymphoma?
June’s Ophthalmology

Matsuo et al. have found that radiation may not necessarily be required to treat biopsy-proven malignant mucosa-associated lymphoid tissue lymphoma of conjunctival origin.

In this prospective, noncomparative interventional case series, 13 patients aged 32 to 68 were given the option of either observation or radiation after biopsy.

Five patients chose radiation of 30 Grays to the remaining conjunctival lesions while the other eight patients were followed without any medication. During the mean follow-up period of 5.4 years, seven of these eight patients without radiation showed spontaneous regression of the conjunctival lesions one to five years after the biopsy. Yearly MRI of the orbit and gallium scintigraphy showed no lesions in all patients. While radiation is generally well tolerated, over the long term it could result in dry eye syndrome or cataract formation.

Consequently, observation may be a viable option after partial or complete resection of low-grade lymphoma of conjunctival origin.

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


Diffuse Structural Damage in Glaucomatous Eyes With Localized Visual Field Abnormalities
American Journal of Ophthalmology

Bagga et al. performed a prospective, cross-sectional analysis of the pattern of structural damage in the macula and peripapillary retinal nerve fiber layer of glaucomatous eyes with localized visual field defects.

The investigators performed automated achromatic perimetry, optical coherence tomography (Stratus; 512
A-scans) of the peripapillary retina and macula and scanning laser polarimetry of the peripapillary RNFL.

Thickness values in the retinal segments associated with the visual field defect (glaucomatous segments) were compared with corresponding segments across the horizontal raphe (nonglaucomatous segments) and age-matched normal controls.

Forty eyes of 40 patients (20 normal; 20 glaucomatous) were enrolled. Mean RNFL thickness measurements using scanning laser polarimetry and optical coherence tomography in the nonglaucomatous segments of glaucomatous eyes were significantly reduced compared with the thickness measurements in the corresponding segments of age-matched normal subjects.

No significant differences in the macular thickness measurements were observed between nonglaucomatous and normal segments. Compared with age-matched controls, RNFL thickness in the nonglaucomatous segment was abnormal in 75 percent of patients with scanning laser polarimetry and in 90 percent of patients with OCT. Macular thickness in the nonglaucomatous segment was abnormal in 55 percent of patients.

The study suggests that diffuse RNFL and retinal ganglion cell loss is present in eyes with localized visual field abnormalities. Detection of localized changes in macular thickness is limited by measurement overlap among normal and glaucomatous eyes.

Multifocal Electroretinogram Reveals Transient Reduction in Retinal Function After PDT
American Journal of Ophthalmology

Lai et al. evaluated the early changes in retinal function after PDT using multifocal electroretinogram in a prospective interventional case series of 17 eyes from 17 patients scheduled for standard PDT with verteporfin (Visudyne).

Patients’ diagnoses included CNV secondary to AMD, idiopathic CNV, myopic CNV, polypoidal choroidal
vasculopathy and central serous chorioretinopathy.

Serial mfERG recordings were performed before PDT and at intervals following PDT. The first-order kernel first negative peak (N1) and first positive peak (P1) mfERG response from the central 0 to 7 degrees and peripheral 7 to 25 degrees were grouped and analyzed. The mean response amplitudes and peak latencies of the mfERG recordings were compared longitudinally.

There were statistically significant reductions in the mean N1 response amplitude for the central group at four days and two weeks after PDT, in the mean P1 response amplitude for both the central and peripheral groups at four days and for the central group at two weeks after PDT. There were also statistically significant increases in the mean P1 response latencies at four days and at two weeks after PDT for the central group, and at four days after PDT for the peripheral group. At one month after PDT, no significant differences in the N1 and P1 mean response amplitudes and peak latencies were observed compared with pre-PDT mfERG.

It appears that transient impairments in retinal function up to two weeks after PDT were noticed by reduction in response amplitudes and delay in peak latencies of mfERG. These may explain the common adverse event of subjective visual disturbance early after PDT with normal findings in visual acuity and ophthalmoscopy.

The Short-Term Visual Effects of Viagra in Healthy Young Men
American Journal of Ophthalmology

Jagle et al. studied the short-term visual effects of a single 100-milligram dose of sildenafil citrate (Viagra) in healthy males.

In a randomized double-blind placebo-controlled clinical trial of drug effects, 20 men between the ages of 20 and 40 were treated with either a placebo or 100 milligrams of sildenafil. Visual function tests included electroretinogram recordings, on/off and 3.3 hertz flicker-ERG recordings, anomaloscope matches and measurements of cone contrast sensitivities and transient tritanopia.

Most visual parameters did not differ between the sildenafil and placebo groups. However, statistically significant increases in sensitivity during transient tritanopia were observed as well as significant prolongations in the implicit times of scotopic a-wave, photopic b-wave and 3.3 Hz flicker a-wave and b-wave ERG recordings. The magnitude of the differences correlated with peak sildenafil plasma concentration.

Although rod amplitudes of the ERG recordings tended to be higher and cone amplitudes lower in the sildenafil group after drug ingestion, the differences were not significant.

There were no reports of visual side effects and all electrophysiological and psychophysical parameters returned to the normal range within 24 hours.

A single oral dose of 100 mg of sildenafil given to healthy young males led to small but statistically significant transient changes of outer and inner retinal function, as detected by ERG and psychophysical methods.
Although the acute effects were fully reversible within 24 hours, it would be worthwhile to compare them with those induced by other drugs that inhibit phosphodiesterase types 5 and 6.

Using the Artificial Silicon Retina Chip for the Treatment of Vision Loss Due to Retinitis Pigmentosa
Archives of Ophthalmology

When retinitis pigmentosa patients have relatively intact outer retinal layers, electrical stimulation of those structures may produce vision.

In a pilot study, Chow et al. investigated the safety and efficacy of an artificial silicon retina chip (ASR) that was implanted into the subretinal space to treat vision loss from retinitis pigmentosa. The silicon-based chip—which is 2 millimeters in diameter and contains 5,000 microelectrode-tipped microphotodiodes that are powered by incident light—was implanted into the right eye of six patients while the left eye served as the control.

In follow-up ranging from six to 18 months, all ASRs functioned electrically. No patient showed signs of implant rejection, infection, inflammation, erosion, neovascularization, retinal detachment or migration. Visual function improvement occurred in all patients and included unexpected vision improvement in retinal areas distant from the implant. Subjective improvement included improved perception of brightness, contrast, color, movement, shape, resolution and visual field size. No significant safety-related side effects were observed.

The observation of retinal visual improvement away from the implant site suggests a possible generalized neurotrophic-type rescue effect on damaged retina from the presence of the ASR.

The Prevalence of Refractive Errors Among Adults in the United States, Western Europe and Australia
Archives of Ophthalmology

Kempen et al. estimated the prevalence of refractive errors in people who are at least 40 years old.

The researchers obtained counts of phakic people with and without spherical equivalent refractive error in the worse eye greater than or equal to +3 D, less than or equal to –1 D, and less than or equal to –5 D from six population-based eye surveys in strata of gender, race/ethnicity and five-year age intervals (29,281 people).

Pooled age-, gender- and race/ethnicity-specific rates for each refractive error were applied to the corresponding stratum-specific U.S., Western European and Australian populations.

Among year 2000 populations aged 40 or older in the United States, Western Europe and Australia, the estimated crude prevalence for hyperopia greater than or equal to +3 D was 9.9 percent, 11.6 percent and 5.8 percent (11.8, 21.6 and 0.47 million people), respectively; the estimated crude prevalence for myopia less than or equal to –1 D was 25.4 percent, 26.6 percent and 16.4 percent (30.4, 49.6 and 1.3 million people), respectively, of whom 4.5 percent, 4.6 percent and 2.8 percent (5.30, 8.5 and 0.23 million people), respectively, had myopia less than or equal to –5 D. Projected prevalence rates for 2020 were similar.

In conclusion, refractive errors affect approximately one-third of people aged 40 or older in the United States and Western Europe, and one-fifth of Australians in that age group.

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

Management of Ocular Surface and Tear Film in LASIK
Journal of Refractive Surgery

The status of the ocular surface and tear film can impact LASIK outcomes in terms of potential complications, refractive outcomes, optical quality, patient satisfaction and the severity and duration of dry eye.

After conducting a literature review, Albietz and Lenton identified best practice management strategies to optimize management of the ocular surface and tear film before, during and after LASIK. Among their findings:

  • Dry eye before surgery and female gender constitute risk factors for developing chronic dry eye after LASIK.
  • Topical anesthetics should be used just before surgery to minimize epithelial damage during surgery.
  • Ocular surface trauma during LASIK can be reduced by using appropriate lubricants and minimizing physical interference with the ocular surface.
  • Artificial tears are a critical component of the ocular surface and tear film management strategy.

The researchers call for controlled prospective trials to define the magnitude and severity of dry eye associated with LASIK; screening methods and patient profiling to better identify appropriate patients; and studies to investigate optimal surgical techniques to minimize damage to the ocular surface and tear film.

Radiotherapy for Recurrent CNV Complicating AMD
British Journal of Ophthalmology

A study by Marcus et al. looking at radiotherapy for recurrent CNV in AMD indicates a palliative benefit with higher fraction sizes and doses.

In this nonrandomized, uncontrolled study, 18 consecutive eyes received external beam irradiation with seven fractions of 2 Grays. The next 16 consecutive eyes received external beam irradiation with five fractions of 3 Gy. Main outcome measures included changes in visual acuity and contrast sensitivity.

While the 3 Gy fraction group lost fewer lines of visual acuity than the 2 Gy fraction group at three- and six-month follow-up, the difference was not maintained at one year. There was no evidence of fluorescein angiographic stabilization of the CNV for either group, and no significant complications were observed.

The researchers conclude that since the radiobiologic differences between low- and high-fraction size groups are modest and correlate with the modest and short-term difference in visual outcomes, it would be of value to study radiotherapy for this condition using fraction sizes of 4 Gy or higher.

Pediatric Trends: The Increasing Incidence of Paintball Injuries


Eye injuries caused by paintballs are an unrecognized cause of severe injury and permanent visual loss in children—particularly among boys who play informally in unsupervised settings and without eye protection.

After reviewing previously unpublished data from the U.S. Consumer Product Safety Commission, David A. Listman found that the incidence of paintball eye injuries treated in emergency departments increased from an estimated 545 in 1998 to more than 1,200 in 2000, with the pediatric population making up more than 40 percent of these cases.

An English-language literature review revealed large numbers of hyphemas, retinal detachments, cataracts, corneal abrasions, vitreous hemorrhages and commotio retinae.

The author advocates restricting the availability of these “very dangerous but easily acquired guns and ammunition” and urges practitioners to counsel young people and their caregivers about appropriate eye protection. He also calls for more parental supervision.

Supplemental Oxygen Improves Diabetic Macular Edema
Investigative Ophthalmology and Visual Science

Nguyen et al. found evidence to support their theory that hypoxia plays a critical role in the development and maintenance of diabetic macular edema.

In this study, the researchers treated five chronic DME patients with supplemental oxygen, determining the effect on visual acuity and retinal thickness.

After three months of 4 liters per minute of inspired oxygen by nasal cannula, nine of nine eyes with DME at baseline showed a reduction in thickness of the center of the macula. Foveal thickness above the normal range was reduced by an average of 43.5 percent, excess foveolar thickness was reduced by an average of 42.1 percent, and excess macular volume was reduced by an average of 54 percent. Three eyes demonstrated improvement in visual acuity by at least 2 lines, one improved by slightly less than 2 lines and five eyes showed no change. Three months after discontinuing oxygen therapy, five of the nine eyes showed increased thickening of the macula.

The authors conclude that their theory on retinal hypoxia and DME deserves further exploration in a controlled study.

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