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Journal Highlights
New Findings from Ophthalmology, AJO and Archives
 
 

February’s Ophthalmology:

Uncertainty Remains Over the Long-Term Stability of Hyperopic LASIK Refractive Corrections

Measuring CCT: Readings Vary Over a Three-Month Period

Ocular Hypertension Patients With Thinner Corneas Show Thinner Retinal Nerve Fiber Layers

Reducing IOP in POAG Patients: Bimatoprost vs. Latanoprost

Major Ocular Morbidity Associated With Outbreak of Rift Valley Fever

January Ophthalmology:

Lowering IOP in Glaucomatous Eyes May Partially Restore Retinal Ganglion Cell Function

In Iceland, Geographic Atrophy Is the Predominant Type of AMD

OCT Illuminates Process in Leber’s Hereditary Optic Neuropathy

Minnesota Study Finds 1 Percent Incidence of Childhood Exotropia

January AJO:

Artifacts Produced by OCT of Retinal Pathology

Sociodemographic Factors and AMD in Latinos: The Los Angeles Latino Eye Study

OCT Scanning in the Detection of Glaucomatous Damage—Study 1

OCT Scanning in the Detection of Glaucomatous Damage—Study 2

Archives:

Treating Pediatric Myopia

AMD Detection Using Images From Standard Film Fundus Cameras and Nonmydriatic Digital Cameras

Intravitreal Voriconazole

Roundup of Other Journals:

Do Older Drivers With Glaucoma Cause More Car Accidents?

The Aqueous Outflow System as a Mechanical Pump

Mass Treatment With Single-Dose Azithromycin for Trachoma

Previews

Uncertainty Remains Over the Long-Term Stability of Hyperopic LASIK Refractive Corrections
Ophthalmology
February’s issue

A study by Jaycock et al. questions the long-term stability of hyperopic LASIK refractive corrections.

For five years, the researchers followed 33 patients who underwent LASIK for hyperopia. The preoperative spherical equivalent at the spectacle plane was +3.58 D and the attempted mean spherical correction at the corneal plane was +3.81 D.

At five years, hyperopic LASIK offered acceptable predictability for the correction of low degrees of hyperopic refractive errors, with 22 out of 31 eyes within +/–1 D of the intended correction for treatments between +1 D and +3 D. However, predictability for higher-order correction was less acceptable, with six out of 16 eyes within +/–1 D of the intended correction for treatments between +3.5 D and +6 D. Additionally, there was an increase in hyperopia over the five-year follow-up period that was more than would be expected with age.

The authors conclude that while hyperopic LASIK may be moderately effective for correcting low degrees of hyperopia, its long-term stability remains questionable.

Measuring CCT: Readings Vary Over a Three-Month Period
Ophthalmology
February’s issue

In glaucoma, the relationship between central corneal thickness and IOP has been the subject of much debate. The Ocular Hypertension Treatment Study, for example, recently suggested a link between CCT and the risk of developing primary open-angle glaucoma. If CCT does, in fact, play a predictive role, then obtaining an accurate measurement is essential.

Wickham et al. studied the variability of CCT measurements taken within a six-month period and then analyzed the findings using OHTS criteria. The researchers used an ultrasonic handheld pachymeter to measure CCT in 51 patients with glaucoma during two consecutive clinic visits. The readings not only showed a clear fluctuation over a three-month period but demonstrated a systematic bias toward increased corneal thickness being recorded at the second reading of two eyes.

From these findings, the authors suggest that a single reading may not accurately predict risk. Thus, for CCT to become a viable addition to glaucoma risk assessment, more than one reading may be necessary.


Ocular Hypertension Patients With Thinner Corneas Show Thinner Retinal Nerve Fiber Layers

Ophthalmology
February’s issue

A study by Henderson et al. suggests that individuals with ocular hypertension may already have early glaucomatous structural loss not detected by conventional methods.

The researchers explored whether ocular hypertension patients with thinner corneas showed a higher frequency of abnormal results in tests designed to detect loss of retinal nerve fiber layer. In this observational cross-sectional study, one eye from each of 44 ocular hypertension patients and 48 healthy individuals underwent imaging with a commercially available scanning laser polarimeter (GDx VCC). The relationship between GDx VCC retinal nerve fiber layer measurements and central corneal thickness (a risk factor for development of visual field loss among ocular hypertension patients) was examined.

The researchers found that ocular hypertension patients with thicker corneas and healthy controls. 

The researchers conclude that GDx VCC measurements of the retinal nerve fiber layer may indicate early structural glaucomatous damage in ocular hypertension patients.

Reducing IOP in POAG Patients: Bimatoprost vs. Latanoprost
Ophthalmology
February’s issue

In patients with primary open-angle glaucoma, bimatoprost was slightly more efficacious than latanoprost in reducing the 24-hour diurnal IOP. However, the IOP difference between the two groups was small and may not be clinically meaningful.

In this double-masked, crossover comparison, Konstas et al. randomly assigned 44 patients with primary open-angle glaucoma to receive either latanoprost 0.005 percent or bimatoprost 0.03 percent for a seven-week treatment period. Diurnal curve IOPs were measured at the end of the treatment period at two, six, 10, 14, 18 and 22 hours. Following the first treatment period, patients immediately changed to the opposite medicine. Diurnal curve measurements were performed again at the end of this second treatment period.

The largest IOP difference at any time point was 0.9 mmHg at 18 hours. The most common side effect was conjunctival hyperemia, which was less with latanoprost than bimatoprost.

The authors call for further research to clarify the clinical differences and the efficacy and safety issues between these two medicines.

Major Ocular Morbidity Associated With Outbreak of Rift Valley Fever
Ophthalmology
February’s issue

Rift Valley fever is an arthropod-borne viral disease caused by a Bunyaviridae RNA virus that is transmitted to humans through a bite by an infected mosquito or through direct contact with an infected animal.

A major outbreak of the fever occurred in the southwestern region of Saudi Arabia from September to November, 2000, and Al-Hazmi et al. report the major ocular morbidity associated with the disease.

The mean interval between the onset of the fever and visual symptoms in 143 patients with 212 affected eyes ranged from four to 15 days. All affected eyes showed macular or paramacular retinitis at the time of initial assessment. The fever affected the uvea and posterior chorioretinal area and was associated with permanent visual loss due to macular and paramacular scarring, vascular occlusion and optic atrophy.

In addition, the study demonstrated for the first time that Rift Valley fever was associated with transient mild to moderate nongranulomatous anterior uveitis, which often resolved completely without complications.

Reviews

Lowering IOP in Glaucomatous Eyes May Partially Restore Retinal Ganglion Cell Function
Ophthalmology
January’s issue

Several multicenter studies indicate that IOP reduction delays the onset or progression of visual field deterioration in ocular hypertension. Ventura and Porciatti draw on results from the pattern electroretinogram—which uses a stimulus of contrast-reversal gratings rather than uniform flashes of light—to provide a neurophysiological explanation for those findings. Specifically, this pilot study demonstrates that lowering IOP in glaucomatous eyes with early visual field impairment partially restores retinal ganglion cell function.

The investigators reviewed 49 eyes of 25 patients with ocular hypertension or glaucoma undergoing topical treatment to lower IOP.

They found that reducing IOP may result in a significant improvement of pattern electroretinogram amplitude and/or phase, suggesting that the abnormal function of a population of retinal ganglion cells may be at least partially restored. The authors conclude that the pattern electroretinogram may prove to be a useful tool to investigate the neuroprotective effects of IOP-lowering drugs based on retinal ganglion cell function.

In Iceland, Geographic Atrophy Is the Predominant Type of AMD
Ophthalmology
January’s issue

Jonasson et al. report findings from the Reykjavik Eye Study, describing the five-year incidence of early age-related maculopathy and AMD by age and gender in Iceland.

The sample included 1,045 citizens 50 years and older undergoing a baseline examination in 1996, with 88.2 percent of survivors undergoing follow-up in 2001.

The authors found a statistically significant increase in incidence with age for soft drusen, hypopigmentation, hyperpigmentation and early ARM. Results indicated that 10.7 percent of people aged 50 to 59 at baseline and 25.7 percent of those aged 70 to 79 developed hypopigmentation at five years. On the other hand, no one aged 50 to 59 years at baseline developed AMD. Geographic atrophy developed in 4.6 percent of those 70 years and older at baseline, while none in this age group developed exudative AMD.

The authors conclude that in Iceland, the interaction of genetic and environmental or dietary influences may have decreased the risk of neovascularization and increased the risk for geographic atrophy.

OCT Illuminates Process in Leber’s Hereditary Optic Neuropathy
Ophthalmology
January’s issue

Optical coherence tomography technology has again provided insight into an ophthalmic disease process. The device allowed Barboni et al. to quantify retinal nerve fiber layer thickness changes in patients with Leber’s hereditary optic neuropathy, a mitochondrial genetic disorder associated with subacute vision loss.

The researchers analyzed eight patients with early Leber’s hereditary optic neuropathy and 30 with the atrophic form of the disease (E-LHON:  disease duration shorter than six months; A-LHON: duration longer than six months) and compared them with 75 age-matched controls.

On the basis of OCT data, the retinal nerve fiber layer was thickened in E-LHON and severely thinned in A-LHON.

The retinal nerve fiber layer was partially preserved in A-LHON with visual recovery.

The authors found that the temporal fibers (papillomacular bundle) were the first and most severely affected, and the nasal fibers seemed to be partially spared in the late stage of the disease.

Their findings suggest that the window of opportunity for rescuing the papillomacular bundle is very limited.

Minnesota Study Finds 1 Percent Incidence of Childhood Exotropia
Ophthalmology
January's issue

In a population-based study conducted in Olmsted County, Minn., Govindan et al. found a cumulative incidence of childhood exotropia of approximately 1 percent for all children younger than 11 years.

The researchers used a population-based medical record retrieval system, identifying all pediatric residents (less than 19 years old) diagnosed with an exodeviation from 1985 to 1994.

Records revealed 250 cases of childhood exotropia, with an annual age- and gender-adjusted incidence of 64.1 per 100,000 patients younger than 11 years, with a significant decrease in the incidence during the teenage years.

The investigators found that the most commonly diagnosed forms of childhood exotropia in the setting of an abnormal central nervous system were intermittent exotropia and convergence insufficiency.

From these findings, the authors estimate 43,103 new cases of childhood exotropia will occur each year in the United States, with more than half presumably developing the most common form—intermittent exotropia.

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.

Artifacts Produced by OCT of Retinal Pathology
American Journal of Ophthalmology
January’s Issue

Optical coherence tomography is now frequently performed for a variety of ocular disease processes, although its accuracy and inadequacies still are being debated. Ray et al. studied the frequency and type of OCT fast macular thickness map scan artifacts, and then tried to determine whether these artifacts depend on patient diagnosis, demographics and ocular therapy.

In this retrospective observational case series over a three-week period, 171 eyes were analyzed in the vitreoretinal faculty service at Duke University. The relationships between OCT scan artifacts and ocular diagnosis, ocular treatment and patient demographics were determined. Logistic regression was used to relate OCT scan artifacts simultaneously with ocular diagnosis and treatment.

Retinal scan artifacts, though not observed in normal eyes, were identified frequently in eyes with macular pathology.

Artifacts were observed in 43.2 percent of all scans, and of these, an erroneous retinal thickness measurement was obtained in 62.2 percent. Six types of OCT surface map artifacts were observed. Of these, inner and outer retinal misidentification, degraded image artifact, and “off center” artifact were significantly associated with central thickness calculation errors (P < 0.001). Neovascular AMD, full thickness macular hole and photodynamic therapy were all associated with increased artifact (P = 0.002, 0.022, and < 0.001, respectively).

OCT scan artifacts are seen surprisingly frequently, adversely affect retinal thickness measurements in a high proportion of cases and are diagnosis-dependent.

Ophthalmologists need to recognize these artifacts in order to improve retinal thickness measurement accuracy, and to prevent faulty treatment decisions that are based on inaccurate retinal thickness measurements.

Sociodemographic Factors and AMD in Latinos: The Los Angeles Latino Eye Study
Archives of Ophthalmology
January’s Issue

The Los Angeles Latino Eye Study Group has initiated a series of studies including this population-based, cross-sectional study to assess the association of various sociodemographic factors and early and advanced (geographic atrophy, exudative) AMD in Latinos.

The study population included Latinos (primarily Mexican-American) aged 40 years and older living in La Puente, Calif.

Sociodemographic factors, obtained from an interviewer-administered questionnaire, included age, gender, Native American ancestry, acculturation, country of birth, employment, income, marital status, health insurance and level of education.

All participants underwent complete ophthalmic examination. AMD was diagnosed from stereoscopic macular photographs. Univariate and multivariable logistic regression was used to assess associations between sociodemographic factors and AMD.

Gradable retinal photographs from 5,875 participants were included. Mean participant age was 54.9 years, 42 percent were male and 5 percent had Native American ancestry.

Stepwise logistic regression analyses indicated that age, gender and being born in the United States were associated with early AMD. Native American ancestry was then associated with any advanced AMD and geographic atrophy.

Family history of AMD was also associated with geographic atrophy. Acculturation was not associated with AMD.

The authors conclude that independent risk indicators for the various types of AMD include older age, male gender, being born outside the United States, Native American ancestry and a family history of AMD. These risk factors were independent of other possible behavioral factors such as smoking and alcohol consumption.


OCT Scanning in the Detection of Glaucomatous Damage—Study 1
Archives of Ophthalmology
January’s Issue

Several cross-sectional studies have demonstrated the capability of optical coherence tomography to detect glaucomatous changes. OCT enables posterior pole scanning of three regions: macula, peripapillary and optic nerve head. Wollstein et al. compared the ability of each region to detect glaucomatous damage.

Their retrospective observational cross-sectional study included 37 normal (37 subjects) and 37 glaucomatous eyes (26 subjects). Eyes had comprehensive ocular examination, reliable and reproducible Swedish interactive thresholding algorithm standard 24 to 2 perimetry, and Stratus OCT scanning of macula, peripapillary and optic nerve head regions on the same visit.

Optic nerve head appearance wasn’t part of the inclusion criteria. The main outcome measure was area under receiver operator characteristic curves (AROCs), which was calculated for each scanning region for distinguishing between normal and glaucomatous eyes. The highest AROCs for distinguishing between groups were for optic nerve head parameters and peripapillary nerve fiber layer thickness followed by macular volume and thickness. A statistically significant difference existed in optic nerve head and nerve fiber layer AROCs when compared with macular AROCs. The authors conclude that OCT optic nerve head and nerve fiber layer parameters provided similar discrimination capabilities between healthy eyes and those of glaucoma patients and superior discrimination capabilities when compared with macular parameters.

OCT Scanning in the Detection of Glaucomatous Damage—Study 2
Archives of Ophthalmology
January’s Issue

In a similar study, Medeiros et al. compared the ability of OCT retinal nerve fiber layer, optic nerve head and macular thickness parameters to differentiate between healthy eyes and eyes with glaucomatous visual field loss in an observational case-control study.

The study included 88 patients with glaucoma and 78 healthy subjects. All patients underwent optic nerve head, retinal nerve fiber layer thickness and macular thickness scans with Stratus OCT during the same visit. Receiver operating characteristic curves and sensitivities at fixed specificities were calculated for each parameter. A discriminant analysis was performed to develop a linear discriminant function designed to identify and combine the best parameters. This linear discriminant function was subsequently tested on an independent sample consisting of 63 eyes of 63 subjects (27 glaucomatous and 36 healthy individuals) from a different geographic area.

No statistically significant difference was found between the areas under the receiver operating characteristic curves (AUC) for the retinal nerve fiber layer thickness parameter with largest AUC (inferior thickness) and the optic nerve head parameter with largest AUC (cup/disk area ratio). The retinal nerve fiber layer parameter inferior thickness had a significantly larger AUC than the macular thickness parameter with largest AUC (inferior outer macular thickness). A combination of selected retinal nerve fiber layer and optic nerve head parameters resulted in the best classification function for glaucoma detection with an AUC of 0.97 when applied to the independent sample.

The authors conclude that retinal nerve fiber layer and optic nerve head measurements had the best discriminating performance among the several Stratus OCT parameters. A combination of optic nerve head and retinal nerve fiber layer parameters improved the diagnostic accuracy for glaucoma detection using this instrument.

Treating Pediatric Myopia
Archives of Ophthalmology
2004;122:1667–1674

Siatkowski et al. examined the safety and efficacy of the relatively selective M1 antagonist pirenzepine in altering the progression of myopia in children aged 8 to 12 years.

One hundred seventy-four patients were randomized in a 2:1 fashion to receive either 2 percent pirenzepine gel or placebo twice daily in each eye. Over a 12-month period, mean myopic progression in the treated group was 0.26 D compared with 0.53 D in the control group (P < 0.001). Antimuscarinic side effects (e.g., cycloplegia and mydriasis) severe enough to warrant withdrawal from the trial occurred in only 4 percent of pirenzepine-treated patients.

In summary, 2 percent pirenzepine ophthalmic gel reduced myopic progression by 50 percent compared with placebo over a one-year period. The safety profile was excellent, and this appears to be a promising pharmacologic treatment for pediatric myopia.


AMD Detection Using Images From Standard Film Fundus Cameras and Nonmydriatic Digital Cameras

Archives of Ophthalmology
2004;122:1642–1646

Klein et al. compared gradings of AMD from digital and stereoscopic film images.

Exact agreement of digital and stereoscopic film images taken through pharmacologically dilated pupils was 91 percent (kappa = 0.85) for the categories of none, early AMD and late AMD. Exact agreement for gradings of digital images taken through dark-adapted pupils compared with gradings of film images was 80 percent (kappa = 0.69). The disagreements for AMD severity level were largely due to 45-degree digital images that could not be graded or were of poor quality. The exact agreement for specific AMD lesions was high with moderate to almost perfect kappa scores.

In summary, these data suggest that digital capture of retinal images may be useful in epidemiological studies where pharmacological dilation of the pupils is not feasible. Further standardization and development of guidelines for using, taking and grading digital images for AMD are necessary to allow comparisons of results among different systems.

Intravitreal Voriconazole
Archives of Ophthalmology
2004;122:1687–1692

Voriconazole is a novel second-generation triazole antifungal agent, potent against a broad spectrum of yeasts and molds. 

Gao et al. assessed intravitreal administration of voriconazole in a rodent model to check for possible toxicity and to determine whether it could be safely employed in the treatment of fungal endophthalmitis.

Using electroretinographic and histologic methods, the researchers found that intravitreal voriconazole up to 25 micrograms per milliliter showed no evidence of toxicity.

Voriconazole appears to be a safe antifungal agent for intravitreal injection in rodents. Following further study, it may be employed in the treatment of human fungal endophthalmitis. Clinical data in humans are forthcoming and will be published early this year.

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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 summaries are edited by the lead authors.

Roundup of Other Journals

Do Older Drivers With Glaucoma Cause More Car Accidents?
Invetigative Ophthalmology & Visual Science
2004;45:3934–3939

Older individuals with glaucoma drive at least as safely as—if not more safely than—glaucoma-free older persons, report McGwin et al.

In this retrospective cohort study, the researchers identified two groups of patients aged 55 and older with and without glaucoma. Motor vehicle collision involvement was obtained from police records.

The researchers found that older drivers with glaucoma had a crash involvement rate approximately 40 to 50 percent lower than that of patients without glaucoma. Drivers with glaucoma self-limited night driving, driving during rush hour, driving on the highway and high-density driving at significantly higher levels than the controls, but this doesn’t appear to explain their reduced risk of crash involvement. 

The findings from this study are in contrast to an earlier report that older drivers with glaucoma had an increased collision risk. This may be due to the design of the present study, which expressed the collision outcome as a rate, thus taking into account person-miles of travel and person-years of travel.

The authors call for further research to evaluate the clinical and functional characteristics of patients with glaucoma to confirm that a subgroup of these people don’t pose a traffic-safety risk.

The Aqueous Outflow System as a Mechanical Pump
Journal of Glaucoma
2004;13:421–438

It has long been thought that aqueous movement through the trabecular meshwork into Schlemm’s canal is a passive process.

However, in this report, Murray A. Johnstone makes the case that aqueous outflow is actually an active phenomenon that is driven by a mechanical pump.

Through findings from the dissecting microscope, light microscopy, scanning electron microscopy, transmission electron microscopy and tracer studies of human and monkey eyes, as well as clinical methods involving slit lamp, gonioscopy and operating microscope examinations of human eyes, the author provides extensive evidence to support his hypothesis.

Laboratory evidence demonstrates the presence of valves in Schlemm’s canal. Elastic and contractile properties of the trabecular meshwork and Schlemm’s canal valves permit pressure transients to cause pulsatile fluid movement through the outflow system. Clinical evidence of pulsatile flow into Schlemm’s canal, from Schlemm’s canal into the collector channels, and from aqueous veins into episcleral veins supports Johnstone’s model.

Johnstone concludes that these mechanisms also provide a means of regulatory feedback to control IOP
and aqueous flow.

Mass Treatment With Single-Dose Azithromycin for Trachoma
The New England Journal of Medicine
2004;351:1962–1971

In a study of a Tanzanian community in which trachoma was endemic, Solomon et al. found that mass treatment with a single dose of azithromycin resulted in a steep decrease of ocular Chlamydia trachomatis.

This decline in infection prevalence continued for two years, at which time only one infection was observed among 842 participants who were tested. The initial study involved 956 of 978 residents of the village of Kahe Mpya, who received either one directly observed oral dose of 20 milligrams of azithromycin per kilogram of body weight or a six-week, twice-daily course of tetracycline eye ointment.

The prevalence of infection fell from 9.5 percent before mass treatment to 2.1 percent at two months and 0.1 percent at 24 months. The quantitative burden of ocular C. trachomatis infection in the community was 13.9 percent of the pretreatment level at two months and 0.8 percent at 24 months.

The authors attribute these results  to high baseline treatment coverage, and conclude that one round of high-coverage mass treatment with azithromycin can interrupt the transmission of a leading cause of blindness.

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

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