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June 2007

Journal Highlights
New Findings from Ophthalmology, AJO and Archives

June's Ophthalmology:

June's American Journal of Ophthalmology:

April's Archives of Ophthalmology:

Roundup of Other Journals:


Sodium Hyaluronate 1 Percent vs. Hydroxypropyl Methylcellulose 2 Percent After Cataract Surgery
June’s Ophthalmology

Rainer et al. detailed the course of postoperative IOP with sodium hyaluronate 1 percent (Healon) and hydroxypropyl methylcellulose (HPMC) 2 percent (OcuCoat) in the first eight hours after cataract surgery.

Both caused significant IOP increases, with the higher IOP increase associated with HPMC. This group also showed more frequent IOP spikes to 30 mmHg (33 percent vs. 13 percent).

The highest mean IOP increase in the HPMC group occurred at two hours postoperatively, in contrast to eight hours postoperatively in the sodium hyaluronate group. At 20 to 24 hours after cataract surgery, neither group demonstrated a significant IOP increase or an IOP spike to 30 mmHg or higher.

The authors conclude that a single measurement at six hours postoperatively could detect all IOP spikes in the sodium hyaluronate group, while a single measurement at two hours postoperatively could detect two-thirds of IOP spikes in the HPMC group—a relevant finding given the outpatient nature of the surgery.

Bacterial Keratitis Linked to Poor Graft Survival and Visual Outcome After Penetrating Keratoplasty
June’s Ophthalmology

In a retrospective case series, Wagoner et al. found that bacterial keratitis represents a serious postoperative complication of penetrating keratoplasty. The infection is associated with poor graft survival and visual outcome.

In addition, the authors observed that retained sutures constitute a key risk factor in the development of late-onset bacterial keratitis after prophylactic topical antibiotics are discontinued.

The study involved 102 eyes treated for culture-positive keratitis at a single center between 1998 and 2002. The authors found that the best graft survival was in eyes with penetrating keratoplasty for keratoconus, while the poorest was for previously failed grafts.

Factors associated with an increased risk of graft failure included surgical indication for penetrating keratoplasty, increasing patient age, smaller donor and recipient graft size, history of previous microbial keratitis or endothelial rejection episodes, and coexisting glaucoma.

Given these findings of this case series, the authors call for a prospective study to determine the role of chronic antibiotic prophylaxis and the timing of suture removal in these penetrating keratoplasty cases.

Artisan Phakic Intraocular Lens Safe, Effective After 10 Years
June’s Ophthalmology

Tahzib et al. conducted a 10-year retrospective follow-up study of the Artisan phakic intraocular lens (PIOL) for the correction of moderate to high myopia.

The results of the study indicate this PIOL is both stable and predictable in the long term. However, the researchers also emphasize that these findings are valid only when strict inclusion criteria are applied.

The original 49 patients (89 eyes) had a stable refraction during the previous two years, an anterior chamber depth of 3 mm or more, an endothelial cell density count of 2,000 cells/mm2 or more, a normal pupil and iris configuration and no history of glaucoma or uveitis.

Ten years after implantation, the researchers found there was no significant change in mean spherical equivalent, and 68.8 percent of eyes were within 1 D of intended correction.

In addition, 93.3 percent reached a BCVA of 20/40 or better, and 82 percent reached an uncorrected visual acuity of 20/40 or better.

European Eye Study Links Cigarette Smoking to Age-Related Macular Degeneration
June’s Ophthalmology

The population-based European Eye Study (EUREYE) investigated 4,750 randomly sampled people over age 65 and examined the association between cigarette smoking and age-related macular degeneration.

The findings by Chakravarthy et al. confirmed the risk of AMD from smoking and specifically demonstrated the association between smoking and geographic atrophy, as well as the increased risk of blindness through bilateral involvement. Compared with people with unilateral AMD, those with bilateral AMD were more likely to have been heavy smokers in the previous 25 years. The attributable fraction for AMD due to smoking was 27 percent. On the positive side, study results indicated that long-term cessation reduced smoking’s adverse effects.

The authors call for a public education campaign to raise awareness of the risks associated with smoking and the benefits of quitting.

Verteporfin and Intravitreal Bevacizumab Combination Treatment
June’s Ophthalmology

In a study of patients with choroidal neovascularization due to age-related macular degeneration, Lazic and Gabric demonstrated that improvements in BCVA and reduction of central foveal thickness after one month and their maintenance over three months are clinically more important after verteporfin photodynamic therapy (PDT) combined with intravitreal bevacizumab than after the individual use of either therapy.

In this randomized, controlled, pilot clinical trial, the authors studied 165 eyes of 165 patients between the ages of 60 and 87. They were assigned to either a single PDT session with verteporfin, a single administration of intravitreal bevacizumab or a combination of both. After one month, the researchers observed an improvement from baseline larger than 0.2 logMAR in BCVA in one verteporfin PDT patient, 16 intravitreal bevacizumab patients and 29 combination patients. At three months, this improvement was still seen in 22 patients receiving the combined treatments. The authors call for larger, long-term prospective trials to confirm these results.

American Journal of Ophthalmology

Biometry Formulae and IOL Types in Extreme Hyperopia
June’s AJO

MacLaren et al. audited IOL power predictions for cataract surgery in extreme hyperopia and compared the accuracy across different biometry formulae and IOL types.

A retrospective analysis was performed of 76 eyes from 56 patients undergoing cataract surgery with IOLs ranging in power from 30 to 35 D. Axial lengths, corneal powers and anterior chamber depths were measured with ultrasound or optical methods, and IOLMaster software was used to predict the refractive outcome for each IOL used. Differences between the predicted and actual postoperative refraction were then analyzed for each formula.

In practice, 55 percent of patients were within 1 D of the refraction predicted by their surgeon. In theory, the Haigis formula would have given the smallest mean refractive error, followed by the Hoffer Q, Holladay 1 and SRK/T formulae. The Haigis formula overpredicted the lens power required, which would have generated a myopic result. The other formulae underpredicted the lens power required and would have generated a hyperopic result. There was a significant difference between lens designs: the Haigis was more accurate for open-loop, whereas the Hoffer Q was more accurate for plate-haptic lenses.

The Haigis formula is the most accurate in extreme hyperopia. A consistent difference between open-loop and plate-haptic lenses suggests that the haptic design may influence the effective lens position in very small eyes.

Effect of Silicone Optic Edge Design on Posterior Capsular Opacification
June’s AJO

Buehl et al. compared the posterior capsular opacification (PCO) inhibiting effect of the round anterior and sharp posterior optic edge profile of the Clariflex silicone IOL with that of the double-round edge profile of the Phacoflex SI40 silicone IOL over a period of three years.

Fifty-two patients with age-related cataracts (104 eyes) were included in this prospective, randomized, double-masked, bilateral clinical trial.

Each patient received an SI40 IOL (round edges) in one eye and a Clariflex IOL with sharp posterior optic edges in the other eye. Regular follow-up examinations were performed over a three-year period with digital retroillumination images taken of each eye. The amount of PCO was subjectively assessed with the slit lamp and objectively assessed by image analysis software (Automated Quantification of After-Cataract) for up to three years after surgery.

The Clariflex lens showed markedly less PCO at one, two and three years after surgery. The mean Automated Quantification of After-Cataract PCO score was 1.39 for the SI40 and 0.56 for the Clariflex lens after one year. The authors estimate this score at 1.64 and 0.57 after two years and at 2.04 and 0.64 after three years. After three years, there were five cases of Nd:YAG laser capsulotomy in the SI40 group compared with one case in the Clariflex group.

The Clinical Diagnosis of Microbial Keratitis
June’s AJO

Dahlgren et al. evaluated the ability of ophthalmologists to predict the laboratory results of presumed microbial keratitis and then further explored which findings might influence diagnostic prognostication.

In this prospective, cross-sectional study, 15 ophthalmologists completed study forms at the initial presentation of patients with presumed microbial keratitis. After predicting the category of microbial recovery, clinicians submitted corneal scrapings for masked laboratory processing. The relative effects of ocular inflammatory signs on correct microbial diagnosis were explored with Poisson regression.

The clinical examiners correctly predicted the presence or absence of microbial recovery in 76 percent of 104 ulcerative keratitis cases and successfully distinguished among bacterial, fungal and amoebic keratitis for 73 percent of 74 culture-positive infections, although only 42 percent were subcategorized properly. The positive predictive value of clinical diagnosis was 65 percent for 20 eyes with Pseudomonas keratitis, 48 percent for 38 other bacterial keratitis cases, 45 percent for 13 fungal keratitis cases and 89 percent for nine Acanthamoeba keratitis cases. The recognition of Pseudomonas keratitis significantly improved by the occurrence of a larger infiltrate, and correctly predicting Acanthamoeba keratitis was enhanced by observing a ring infiltrate. Antimicrobial use before referral significantly confused the clinical diagnosis and hampered microbial recovery.

The authors conclude that established Pseudomonas keratitis and Acanthamoeba keratitis can be suspected before laboratory confirmation, but overlapping inflammatory features and recent empiric antimicrobial treatment limits etiologic recognition of most microbial corneal infections.

Ultrastructural Findings After Intravitreal Injection of Bevacizumab
June’s AJO

Peters et al. examined the ultrastructural effect of intravitreal bevacizumab on primate eyes with particular emphasis on choriocapillaris endothelial cell fenestration. Four cynomolgus monkeys received an intravitreal injection of 1.25 mg bevacizumab. The eyes were enucleated and prepared for light and electron microscopy on days one, four, seven and 14, and compared with control eyes.

Choriocapillaris endothelial cell fenestrations were significantly reduced after intravitreal injection of bevacizumab. Fenestration was lowest on day four and increased again from days seven to 14, but was still significantly lower than in the control. Densely packed thrombocytes and leukocytes regionally occluded the choriocapillaris lumen of treated eyes. On day one, an increased number of leukocytes filled in the choriocapillaris lumen. Photoreceptors were damaged in two of 40 light microscopic sections. On days one to seven, choroidal melanocytes contained giant melanosomes. None of these described features was found in controls.

The authors conclude that intravitreal bevacizumab causes ultrastructural changes in the choriocapillaris of primate eyes. A significant reduction of choriocapillaris endothelial cell fenestrations is seen as early as 24 hours after injection and their number increases again after two weeks. These findings may play a role in understanding the early clinical effect of intravitreal bevacizumab for macular edema.

Multifocal Posterior Herpetic Necrotizing Retinitis
June’s AJO

Margolis et al. described the clinical features of an acute, inflammatory and progressive retinal necrosis that affects primarily the posterior pole. Twenty-seven eyes of 24 patients diagnosed with and treated for acute retinal necrosis were categorized into two groups according to the predominant location of retinitis at presentation: either in the peripheral retina or in the posterior pole. Clinical features, disease progression, visual outcomes and complications of these two groups were compared.

Fifteen eyes demonstrated the known peripheral retinitis pattern, and 12 eyes exhibited a pattern of retinitis that affected mainly the posterior pole. Eyes with peripheral retinitis showed focal, well-demarcated areas of retinal necrosis in the periphery with rapid circumferential progression and rare involvement of the posterior pole. All eyes with posterior pole retinitis had multifocal deep lesions posterior to the vortex veins at presentation, and half of these eyes had lesions in the macula. These lesions progressed to confluent retinitis in both the periphery and the posterior pole. There was no significant difference between the two groups in the incidence of anterior chamber and vitreous cells, vascular sheathing, retinal hemorrhages or optic disc edema. Patients with posterior retinitis involvement seemed to have a worse visual outcome during the first two years after diagnosis. The Cox proportional hazards model suggested a higher incidence of retinal detachment in patients with posterior retinitis.

The authors have identified two forms of acute retinal necrosis. The pattern of herpetic retinitis that affects predominantly the posterior pole may have a worse visual prognosis and a higher rate of retinal detachment.

Archives of Ophthalmology

Predictive Factors for Corneal Infiltrates With Continuous Wear of Silicone Hydrogel Contact Lenses
April’s Archives

Corneal infiltrates continue to occur while wearing silicone hydrogel lenses despite their dramatically increased oxygen transmissibility. Cheruvu et al. assessed the probability of developing a corneal infiltrate through three years of up to 30-night continuous wear with lotrafilcon A lenses.

Potential risk factors were modeled using survival analysis methods. The unadjusted cumulative incidence of a corneal infiltrate was 5.7 percent at the end of one year, 8.5 percent at the end of two years and 10.3 percent at the end of three years. Corneal staining and limbal redness were significantly associated with the subsequent development of an infiltrative event.

The authors conclude that the probability of remaining free of any corneal infiltrates at the end of three years of continuous wear with lotrafilcon A contact lenses is almost 90 percent. They also emphasize that corneal staining and limbal redness may predict the subsequent development of an infiltrative event.

Prophylaxis of Acute Posttraumatic Bacterial Endophthalmitis
April’s Archives

In a multicenter, double-masked clinical trial, Soheilian et al. examined the role of adjunct intraocular injection of gentamicin and clindamycin in preventing acute posttraumatic bacterial endophthalmitis.

Three hundred and forty-six eyes of 346 patients with penetrating eye injury were randomized to receive a 0.1 ml intracameral or intravitreal injection of 40 µg gentamicin and 45 µg clindamycin vs. intracameral or intravitreal injection of 0.1 ml balanced saline solution as a control.

Endophthalmitis was diagnosed in only one eye (0.3 percent) in the first group and in eight eyes in the control group (2.3 percent). Intravitreal injection was superior to intracameral injection in preventing endophthalmitis.

Independent risk factors associated with acute posttraumatic bacterial endophthalmitis were: retained intraocular foreign bodies (IOFB), presence of afferent pupillary defect and vitreous prolapse. There was significant association between presence of an IOFB and development of endophthalmitis such that the benefit of treatment was observed only in eyes with an IOFB. However, in eyes with no IOFB, the rate of endophthalmitis was similar in cases and controls.

Cardiovascular Disease and Early Age-Related Macular Degeneration in a Multiracial Cohort
April’s Archives

Klein et al. investigated the relationship of subclinical atherosclerotic cardiovascular disease (CVD) and its risk factors to age-related macular degeneration in the Multi-Ethnic Study of Atherosclerosis. This latter study involved 6,176 white, African-American, Hispanic and Asian-American subjects aged 44 to 84 from six U.S. communities and focused on the characteristics of CVD and predicting progression to clinically overt cardiovascular disease.

The authors utilized measurements of subclinical CVD (e.g., ankle-brachial index, carotid artery intima-media thickness, carotid artery plaques and stenosis, Agatston calcium scores, common carotid arterial distensibility and Young’s modulus) as standardized protocols. Fundus images were graded using the Wisconsin Age-Related Maculopathy Grading System.

Data from this study showed few relationships between serum lipid levels and subclinical CVD with early AMD in the whole cohort. While controlling for age, sex, race/ethnic group and study location, early AMD was associated with the presence of echolucent carotid artery plaque in the whole cohort. Greater intima-media thickness, a marker of atherosclerosis, was found to be associated with early AMD in whites. Other interactions of race/ethnicity and early AMD were found for increasing severity of maximum carotid artery stenosis and subclinical CVD severity.

The authors conclude that there are few associations between subclinical CVD and CVD risk factors with early AMD. The differing associations of early AMD with some signs of subclinical atherosclerotic CVD among the four racial/ethnic groups suggest that care must be taken in generalizing from one racial/ethnic group to another.

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

Retinal Detachment–Induced Photoreceptor Apoptosis and Role of Monocyte Chemoattractant Protein
Proceedings of the National Academy of Sciences

Nakazawa et al. used an experimentally induced model of retinal detachment (RD) in mice to show that monocyte chemoattractant protein (MCP-1) is a critical mediator of photoreceptor apoptosis, which is a major cause of visual loss in several retinal disorders. The investigators demonstrated that MCP-1 levels rapidly rise in Müller glial cells after RD and thus lead to an increased number of macrophage/ microglia in the injury site.

In addition, the acute blockade of MCP-1 with a functionally blocking antibody or deletion of this gene in mice almost completely eliminates RD-induced photoreceptor apoptosis. This cytotoxic effect is a result of oxidative stress produced by activated macro-phage/microglia—as opposed to a direct effect of MCP-1 on the cultured photoreceptors. Deleting the gene for MCP-1 almost completely eliminated the infiltration of macrophage/microglia after RD and protected photoreceptors from RD-induced apoptosis.

The authors conclude that blockade of MCP-1 may open new therapeutic approaches to treat photoreceptor death in relation to retinal disorders and other central nervous system conditions that share this etiology.

Infectious and Noninfectious Keratitis Following LASIK Treatment
Journal of Cataract and Refractive Surgery

Moshirfar et al. classified several noninfectious causes of post-LASIK keratitis and compared them with infectious etiologies. The investigators reviewed charts of 5,618 post-LASIK patients (10,477 eyes).

They found post-LASIK keratitis in 279 eyes. Keratitis was diagnosed as infectious in 33 eyes (12 percent) and as noninfectious in 246 eyes (88 percent).

The infectious cases included herpes simplex keratitis, adenoviral keratitis and nonviral (bacterial, fungal and parasitic) keratitis. A large majority of the noninfectious cases were classified as diffuse lamellar keratitis, and other cases were labeled staphylococcal marginal hypersensitivity and localized debris-related keratitis. In addition, adenoviral cases have the best visual outcomes overall, while all patients with herpes simplex keratitis lost one to two lines of BCVA.

The authors conclude that patients with infectious keratitis experience much worse visual outcomes than those with noninfectious keratitis.

Orbital Detail With High-Resolution Microscopy Coil MRI
Published online March 2, 2007

Georgouli et al. asserted that high-resolution microscopy coil MRI (HR-MRI) would be ideal in the clinical setting to obtain greater anatomic detail of the eye and orbit.

They maintain that the eye is an ideal organ for HR-MRI because of its wide variation in water content, and its small field of view with multiple tissue diversity.

The HR-MRI was able to obtain images of previously unobserved structures and offered a clear demonstration of underlying pathology. Specifically, the tarsal plate, ciliary body, zonules of the lens, and layers of anterior and posterior globe were clearly depicted.

In addition, the imaging device showed the extraocular muscles, the optic nerve together with its sheath, and the retrobulbar fat and parts of its connective tissue.

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