EyeNet Magazine

Journal Highlights
New Findings from Ophthalmology, AJO and Archives

February’s Ophthalmology:

February’s American Journal of Ophthalmology:

December’s Archives of Ophthalmology:

Roundup of Other Journals:



Adherence to Single-Dose Glaucoma Medication
February’s Ophthalmology

Okeke et al. have found that patient adherence with once-daily prostaglandin therapy for glaucoma is not substantially better than once-daily drops of beta blockers or four-times daily pilocarpine.

For this study, the researchers used the Travatan Dosing Aid that electronically records the time and date of a travoprost dose. Of the 196 patients with evaluable data at three months, 109 (55.6 percent) took more than 75 percent of the expected doses. Those who took less than 50 percent of expected doses showed significantly increased dose taking immediately after the office visit and just prior to the return threemonth visit. In addition, neither patient self-report nor physician estimation of adherence accurately reflected the true behavior as measured by the Travatan Dosing Aid.

The investigators conclude that 44 percent of participants who knew they were being monitored and were provided free medications nevertheless took less than 75 percent of the doses, suggesting that poor patient adherence remains a challenge in providing care to glaucoma patients.

Cataract Surgery Does Not Increase Risk of AMD Progression
February’s Ophthalmology

Data from the Age-Related Eye Disease Study (AREDS) suggest there is no clinically important increased risk of progression to advanced age-related macular degeneration following cataract surgery.

This study involved 4,577 participants (8,050 eyes) from AREDS who had varying degrees of AMD and were followed every six months for up to 11 years. The researchers said this was the only prospective study in which the severity of AMD was documented prior to and following cataract surgery in a large number of cases with more than five years of regular follow-up. The Cox regression model allowed them to examine the effect of covariables on progression to late AMD. An absence of any pattern in the direction of harm indicated there was little evidence cataract surgery increased the risk of progression to late AMD.

The authors conclude that while the risk of advanced AMD does not appear to be accelerated by cataract surgery, patients should still be told of the natural course of AMD.

Complement Factor H Coding Variant Linked to Polypoidal Choroidal Vasculopathy
February’s Ophthalmology

Polypoidal choroidal vasculopathy is a hemorrhagic and exudative macular disease with distinct forms of choroidal vascular abnormalities. A study by Kondo et al. provides evidence that complement factor H (CFH) acts as a susceptibility gene for polypoidal choroidal vasculopathy and that the complement pathway plays a key role in the pathogenesis of this disease.

Using a Japanese population, the researchers genotyped 12 single nucleotide polymorphisms (SNPs) that were highly representative of the common genetic variation in the CFH region and observed the strongest association of the nonsynonymous coding variant I62V (rs800292) with polypoidal choroidal vasculopathy. The evidence for association was weaker for all the other SNPs and became nonsignificant after accounting for I62V in a conditional logistic regression analysis.

The authors conclude that these multiple observed effects are caused by linkage disequilibrium with I62V and that this variant fully accounts for the association signals observed at the set of SNPs examined at this locus—thus providing further understanding into the underlying pathophysiology of polypoidal choroidal vasculopathy.

Genetic and Environmental Links to Aging Visual Function
February’s Ophthalmology

Using a classical twin study, Hogg et al. investigated the relative contribution of genetic and environmental influences to the significant losses in visual function associated with normal aging.

They evaluated cone function in 42 pairs of twins (21 monozygotic and 21 dizygotic, ages 57 to 75) with normal visual acuity. Cone function was evaluated by establishing absolute cone contrast thresholds to flicker (4 and 14 Hz) and isoluminant red and blue colors under steady-state adaptation.

The researchers found a strong genetic contribution to cone absolute threshold, color (red and blue) and flicker (4 and 14 Hz) thresholds. However, the dynamic aspects of adaptation and the rod absolute thresholds demonstrated less genetic input—thus implying a greater potential influence from environmental factors.

They conclude that while many common visual parameters are inherited, other vital neuronal processes are significantly influenced by environmental factors over a lifetime—leading to new possibilities in preventing or delaying visual dysfunction or disease.

American Journal of Ophthalmology

Topical Vitamin A vs. Cyclosporine A for Dry Eye Syndrome
February’s AJO

In a randomized group study, Kim et al. compared the efficacy of vitamin A (retinyl palmitate) eye drops and cyclosporine A eye drops in treating patients with dry eye disease.

A total of 150 patients with defined dry eye disease participated (50 in each treatment group). In three identical clinical trials, patients were treated either twice daily with cyclosporine A 0.05 percent, four times daily with retinyl palmitate 0.05 percent or with neither. Adjunctive treatment with preservativefree artificial tears was undertaken four times daily in all three groups. Corneal fluorescein staining results, Schirmer tear test (without anesthesia) results, tear film break-up time, dry eye symptom score and impression cytologic analysis results were obtained before treatment and at the first, second and third months of treatment.

Both vitamin A and cyclosporine A treatments led to significant improvement in blurred vision, tear film breakup time, Schirmer results and impression cytologic findings in patients with dry eye syndrome, when compared with the control group treated with preservative- free artificial tears alone.

Ocular Trauma From Paintballs
February’s AJO

Alliman et al. described ocular injuries attributable to paintballrelated incidents in a retrospective, interventional case series. The investigators examined 36 eyes of 36 patients who sustained ocular injuries from paintballs. The medical and surgical interventions within the first three days after injury and further treatment after this time period were recorded.

The mean age of the patients was 21 years, 86 percent were male and 97 percent were not wearing eye-protection when injured. The initial BCVA was worse than 20/200 in 78 percent and the mean follow-up interval was 11.7 months.

The most common ocular finding was hyphema in 81 percent. Initially, 20 eyes (56 percent) were managed medically and nine eyes (25 percent) required primary repair of a ruptured globe. Ultimately, 29 eyes (81 percent) had surgical intervention including eight eyes (22 percent) with enucleation. Final visual acuity was 20/40 or better in 13 eyes (36 percent), whereas 18 eyes (50 percent) were worse than 20/200. In addition, visual acuity at initial presentation correlated strongly with final visual acuity.

The authors conclude that paintballrelated ocular injuries are frequently severe and visually devastating. The compulsory use of protective eyewear may have eliminated 97 percent of injuries in this series.

Sutureless Pars Plana Vitrectomy Incisions Still Patent
February’s AJO

Pars plana incisions are commonly performed with small-gauge needles and are frequently left unsutured. Gupta et al. compared the relative competency of pars plana vitrectomy (PPV) sclerotomies in an investigation of cadaveric eyes.

PPV was performed in a control eye and two eyes, each using standard 20-gauge, standard 23-gauge, perpendicular 25-gauge and beveled 25-gauge instrumentation incisions. India ink was applied over a sclerotomy site while the IOP was varied. The presence of

India ink particles along incisions was evaluated by histologic analysis. Spectrophotometric absorbance levels of vitreous aspirates were also measured. India ink particles were not detected in the sutured 20-gauge incisions, either on histology or by spectrophotometry. India ink particles were detected along the entire incision length in one of two eyes with 23-gauge unsutured sclerotomies and confirmed by spectrophotometry. India ink particles were also detected along the entire incision length in one of two eyes with 25-gauge unsutured perpendicular sclerotomies and confirmed by spectrophotometry in both eyes. India ink particles were noted partially along the length in one of the two beveled 25-gauge unsutured eyes, but not detected in either eye by spectrophotometry.

The authors conclude that during the early postoperative period, sutureless vitrectomy incisions may allow entry of ocular surface fluid. These findings may provide a pathophysiologic mechanism for the reported increased risk of endophthalmitis in small-gauge vitrectomy surgery.

Reduced Zinc and Copper Levels in AMD
February’s AJO

Erie et al. measured zinc and copper levels in the retinal pigment epithelium (RPE) and choroid complex, and in the neural retina in subjects with and without age-related macular degeneration.

Eighty-eight donor eyes (44 subjects) were analyzed. After retinal dissection, the RPE and choroid complex were photographed. The RPE and choroid complex were classified into one of four stages as defined by the Age-Related Eye Disease Study. Zinc and copper levels were determined by using an inductively coupled plasma-mass spectrometer. Metal levels from two eyes of the same subject were averaged and treated as one observation.

The mean RPE and choroid complex zinc level in subjects with AMD was reduced 24 percent when compared with that of subjects without AMD. The mean RPE and choroid complex copper level in subjects with AMD was reduced 23 percent when compared with that of subjects without AMD. No difference was detected in retinal zinc and copper levels in subjects with and without AMD.

Reduced RPE and choroid complex zinc and copper levels in AMD eyes suggests that metal homeostasis may play a role in AMD and in retinal health.

Archives of Ophthalmology

Surgical Removal vs. Observation for Subfoveal Choroidal Neovascularization
December’s Archives

Bass et al. examined patients receiving either observation or surgery for subfoveal choroidal neovascularization (CNV) that was idiopathic or associated with histoplasmosis, and examined how the patients differed in preference values assigned to their health and vision status.

Before and after enrollment in the trial of observation vs. surgery, patients rated current vision on a scale from zero (blind) to 100 (perfect vision). They were also asked to rate what they imagined blindness and perfect vision to be like on a scale from zero (dead) to 100 (perfect health). Scores for current vision were converted to a preference value scale (zero representing death and 100 representing perfect health and vision).

In 170 patients, no significant difference existed between observation and surgery arms in median vision preference value at baseline, 12 months or 24 months. Preference values did not differ between arms for subgroups defined by age, unilateral vs. bilateral CNV or good vs. poor baseline visual acuity.

The authors conclude that submacular surgery was no better than observation in preference values patients assigned to their health status, despite previously reported improvements in vision-specific quality of life. Ophthalmologists should consider the effects on different measures of quality of life when considering treatment for patients similar to those in this trial.

Uveal Effusion in Primary Angle-Closure Glaucoma
December’s Archives

Kumar et al. attempted to confirm the presence of uveal effusion in the eyes of Asian patients with primary angle-closure glaucoma (PACG) using ultrasound biomicroscopy (UBM).

Seventy patients with PACG and 12 with acute primary angle closure (APAC) were enrolled. Twenty-eight patients were untreated and 42 patients had a patent laser iridotomy and were being followed-up. Eyes of newly diagnosed PACG and APAC patients underwent UBM scanning before and after laser iridotomy, while those who were on follow- up underwent UBM at recruitment. Uveal effusion was defined as a clear space between the choroid and sclera. Grading was done using standardized photographs as a reference: grade 0 (none), grade 1 (slit-like), grade 2 (bandlike) and grade 3 (obvious).

Eleven of 70 eyes with PACG and three of 12 eyes with APAC were found to have uveal effusion. Among the newly diagnosed PACG eyes, effusion was found in four of 28 before laser iridotomy—only two eyes showed effusion after laser iridotomy. Among previously treated PACG eyes, seven of 42 had effusion. The effusion in all PACG eyes was grade 1, while those with APAC showed effusion of grade 2 or 3.

The authors conclude that subclinical uveal effusion was prevalent in about 15 percent of PACG eyes and about 25 percent of APAC eyes. This confirms a report from Japan wherein the authors reported a 9 percent prevalence of effusion in chronic APAC eyes. The findings in the current study were novel in that untreated eyes with PACG or APAC demonstrated uveal effusion—this has not been reported previously. Although it is not known if uveal effusion is a cause or effect of angle closure, it might help determine those at higher risk of disease progression.

Patching vs. Atropine to Treat Childhood Amblyopia
December’s Archives

The Pediatric Eye Disease Investigator Group compared patching with atropine eye drops in the treatment of moderate amblyopia in children 7 to 12 years of age.

One-hundred ninety-three children with amblyopia were randomized to weekend atropine or patching of the sound eye two hours per day. There was a masked assessment of amblyopic eye visual acuity using the E-ETDRS testing protocol at 17 weeks. Visual acuity had improved from baseline by an average of 7.6 letters in the atropine group and 8.6 letters in the patching group, while the mean difference between groups adjusted for baseline visual acuity was 1.2 letters. This difference met the definition for equivalence. Amblyopic eye visual acuity was 20/25 or better in 15 subjects (17 percent) in the atropine group and 20 subjects (24 percent) in the patching group.

Keratectasia After LASIK
December’s Archives

Meghpara et al. examined the histopathologic and immunohistochemical features of corneal buttons from patients who developed keratectasia after LASIK.

Five keratectasia corneal buttons were obtained during penetrating keratoplasty. Histologic features were examined by hematoxylin-eosin staining using paraffin-embedded sections and by transmission electron microscopy. Immunostaining for alpha1-proteinase inhibitor, Sp1, and matrix metalloproteinases 1, 2 and 3 was performed with two normal human corneas and two corneas with keratoconus as controls.

Central stromal thinning was observed after hematoxylin-eosin staining in all corneas with keratectasia. By transmission electron microscopy, collagen fibril thinning and decreased interfibril distance were observed in the stromal bed. However, no histologic features specific to keratoconus—including Bowman’s layer disruption—were identified in the corneas with keratectasia. Immunostaining intensity and/or pattern for alpha1-proteinase inhibitor and Sp1 in the corneas with keratectasia was comparable to that of normal control corneas but different from that of keratoconus. No significant staining with anti-matrix metalloproteinases 1, 2 and 3 antibodies was observed in either the corneas with keratectasia or the normal controls.

The authors conclude that post- LASIK keratectasia results in collagen fibril thinning and decreased interfibril distance within the residual stromal bed. Discrepant immunohistochemical findings between keratectasia and keratoconus suggest that the pathogenesis of the two conditions differ.

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

Roundup of Other Journals

IOP-Independent Retinal Ganglion Cell Degeneration in Glaucoma
Journal of Neuroscience

Not every case of glaucoma is due to a chronic elevation in IOP. Some patients with glaucoma have IOP in the normal range.

According to Wax et al., a select number of these cases may be attributed to an autoimmune component, which would explain the degen eration of retinal ganglion cells (RGCs) and their axons that cause blindness in glaucomatous optic neuropathy.

The researchers used a novel in vivo tool—experimental autoimmune glaucoma produced by heat shock protein (HSP) immunization—to examine the roles of the immune system in immune privilege, protective immunity or induction of an autoimmune neurodegenerative disease. They found that HSP27 and HSP60 immunization in a Lewis rat induced RGC degeneration and axon loss one to four months later in vivo in a pattern that resembled human glaucoma.

They also found that T-cells activated by HSP immunization induced RGC apoptosis via the release of the inflammatory cytokine FasL. On the other hand, HSP immunization induced activation of microglia cells and upregulation of the FasL receptor in RGCs.

Mean Absolute Prediction Error After Cataract Surgery
Journal of Cataract and Refractive Surgery

Kugelberg and Lunström conducted a nonrandomized study that involved 49 Swedish ophthalmology departments over a five-year period to determine which factors influenced the mean absolute prediction error after cataract surgery. They received reports from eye departments participating in the Swedish National Cataract Register during the month of March from 2000 to 2005 for a total of 23,244 cases. They found that several factors might be related to refraction outcome after cataract surgery.

First, absolute prediction error was related to the study year—becoming smaller the more recent the surgery. Second, they found that lower preoperative visual acuity was associated with larger mean absolute prediction error. Third, in this study, patients with glaucoma had a larger mean absolute prediction error. Fourth, it was significantly more difficult to achieve the target refraction in females than in males. However, when the error was dichotomized, biological sex disappeared as a risk factor. The authors expressed surprise that patients with second-eye surgery did not come closer to the target refraction. Finally, the authors found a significant difference in the mean absolute prediction error among the high-volume ophthalmology departments.

Stem Cells Pervasive in the Limbal Region
Published online Nov. 13, 2008

Majo et al. discussed a model that explains why the limbal region is enriched in stem cells. Their model demon strated that mouse corneal epithelium can be serially transplanted, is self-maintained and contains oligopotent stem cells with the capacity to generate goblet cells when provided with a conjunctival environment.

In addition, the entire ocular surface of the pig contains oligopotent stem cells that can generate colonies of corneal and conjunctival cells. Consequently, the limbus is not the only place for corneal stem cells, and corneal renewal is not different from other squamous epithelia. The authors called the limbus a zone of equilibrium, where the expanding conjunctival and corneal epithelia are challenged with a mechanism similar to tectonic plates. A rupture of the equilibrium results in migration of limbal stem cells onto the cornea.

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

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