American Academy of Ophthalmology Web Site: www.aao.org
New Findings from Ophthalmology, AJO and Archives
November's American Journal of Ophthalmology:
Roundup of Other Journals:
Elevated C-Reactive Protein and Homocysteine Levels Associated With AMD
Previous epidemiological studies evaluating risk factors common to both age-related macular degeneration and cardiovascular disease suggest that both diseases may share a similar etiological mechanism. To explore this hypothesis, Vine et al. evaluated two novel markers of cardiovascular disease: high-sensitivity C-reactive protein (CRP), a marker of systemic inflammation that has been shown to be an independent risk factor and predictor of cardiovascular disease, and plasma homocysteine, a sulfur-containing amino acid formed during methionine metabolism and another independent risk factor for cardiovascular disease.
In a case-control study of 79 affected individuals and 77 unaffected individuals from the AMD Genetic Study Group, elevated CRP and homocysteine levels were found in patients with AMD relative to the unaffected patients. The authors conclude these data indicate an association between elevated CRP and homocysteine levels and point to the role of chronic inflammation and atherosclerosis in the pathogenesis of AMD. They call for further studies to delineate this role.
Chromatic Lenses Effective in Modulating Sensory Photophobia in Essential Blepharospasm
One of the most perplexing sensory symptoms of benign essential blepharospasm is photophobia, with up to 79 percent of patients finding bright light to be the most frequent exacerbating factor of this condition. Yet, its underlying pathophysiology remains a mystery, and no proven, noninvasive treatment currently exists.
In their nonrandomized case control study of 34 patients (24 with benign essential blepharospasm and 10 normal controls), Herz et al. found that blepharospasm patients can achieve significant relief of sensory photophobia with chromatic modulation. Lenses 4, 5, 6 and 7, which filter different wavelengths of light, allowed blepharospasm patients to tolerate a significantly higher intensity of light when compared with no lens. Interestingly, while lens 6 allowed patients to endure a higher intensity of light, the majority of patients preferred lens 7 for symptomatic relief.
Findings from this study suggest the photophobia may be more related to wavelength than to intensity of light exposure. The authors recommend prescribing commercially available lens tint as an adjunct therapy for these patients.
For more, see "Photophobia: Looking for Causes and Solutions."
Long-Term Results of Macular RPE Translocation Surgery in AMD “Disappointing”
A five- to six-year follow-up of four of nine patients with age-related macular degeneration who originally underwent macular retinal pigment epithelium (RPE) translocation surgery for choroidal neovascularization has revealed a further decline in visual acuity and loss of foveal fixation —problems that occurred after the original two-year follow-up results were published.
MacLaren et al. also observed late changes in autofluorescence, increasing over the graft donor site and virtually disappearing over the graft itself. Yet the RPE graft seemed viable when assessed by optical coherence tomography, fluorescein angiography and indocyanine green angiography, and no patient suffered a recurrence of CNV.
The authors conclude that while the long-term results of this pilot study were “disappointing,” a detailed analysis of the events occurring after the initial surgery could provide key insight into the mechanisms of AMD and how RPE grafting could be optimized to achieve future success.
A small case series by Ober et al. has demonstrated that photodynamic therapy with verteporfin in patients with focal fluorescein leaks secondary to central serous chorioretinopathy (CSCR) can cause prompt resolution of leakage from CSCR, which in turn can be associated with rapidly improved vision.
The series involved nine eyes of nine symptomatic patients with acute focal retinal pigment epithelial leaks secondary to CSCR. These individuals were treated with PDT, with BCVA recorded at presentation and follow-up visits. The investigators found that neurosensory detachment and fluorescein leakage resolved in all patients within one month. At six months, mean visual acuity improved from 20/80 to 20/40. Additionally, no patient lost vision or experienced any treatment-related complications.
The authors say that the results warrant further investigation to better understand the risks and benefits of this therapy for individuals with CSCR.
Beta-1 Adrenergic Receptor Polymorphisms May Serve as Determinant of Response of Betaxolol in Glaucoma
In the treatment of systemic hypertension, pharmacogenomic studies of two known beta-1 polymorphisms have shown a correlation between genomic status and response to systemic beta-1 blocking drugs.
Schwartz et al. hypothesized that similar relationships may exist within the eye. They conducted a pilot study of normal volunteers to record the clinical effectiveness of betaxolol and to correlate these results with the genomic data. Betaxolol was chosen because it is the only available beta-1 selective agent, so the effects of the beta-2 receptor theoretically would be minimized. Results indicate that the polymorphisms at codon 389 correlate with baseline intraocular pressure and response to treatment with betaxolol, while the polymorphisms at codon 49 of the receptor were not associated with either variable.
They conclude that the polymorphism at codon 389 may predict short-term response to betaxolol and may serve as a determinant of response to betaxolol and other adrenergic agents in patients with glaucoma who require treatment.
Silicone Oil Removal in Patients With CMV-Related Retinal Detachments
Morrison et al. evaluated the risk indicators leading to retinal redetachment in HIV patients with cytomegalovirus retinitis–related retinal detachments that were repaired with silicone oil and that subsequently underwent oil removal.
In this retrospective, noncomparative, interventional case series, 15 eyes in 14 HIV-infected patients who were diagnosed with CMV retinitis and whose retinal detachments were repaired with silicone oil at a single center were followed from the time of the retinitis diagnosis to the removal of the silicone oil. Patient- and eye-specific data regarding demographic and clinical characteristics were collected retrospectively and statistical analyses were performed to compare differences between the eyes that had retinal detachments following silicone oil removal and the eyes that did not.
Approximately half of the eyes underwent safe oil removal. But eight eyes (53 percent) redetached after a median of four months following oil removal. Cataract surgery performed at the time of oil removal was a statistically significant risk factor for redetachment, and there was a trend for lower CD4 cell counts to be associated with a higher risk of retinal redetachment. The use of a scleral buckle at the time of surgery (either at initial repair or at the time of oil removal) did not reduce the risk of redetachment.
There is an accompanying editorial by Janet Louise Davis, MD.
Tractography Depicts Three Layers of Visual Field Trajectories to the Calcarine Gyri
Yamamoto et al. utilized fiber-tracking by diffusion tensor magnetic resonance imaging (DT-MRI) as a noninvasive in vivo method of white matter fiber-tracking in the human brain. Specifically they used this method to visualize the optic radiation and to determine the clinical applicability.
DT-MRI scans for fiber-tracking were obtained in five healthy volunteers by use of a whole-body 1.5 Tesla imager. DT-MRI data were transferred to an off-line workstation; PRIDE software was used for image analysis. They constructed 3-diopter fiber trajectories by tracking the direction of the fastest diffusion from the lateral geniculate nucleus, and then selected tracts on the basis of anatomical knowledge of the optic radiation.
The authors were able to reconstruct the macroscopic 3-diopter architecture of the three major groups of optic radiation in all subjects. Meyer’s loop depicted by tractography appeared more posterior than the known anatomical locations, although the results on the central and posterior bundles were in agreement. DT-MRI scanning required seven minutes; preliminary images of the optic radiation could be obtained in approximately 20 minutes.
The finding that the fiber-tracking method underestimates the anterior extent of the optic radiations could prove to be an important limitation in the utility of this technique for preoperative planning. The time required for data acquisition and processing makes this method acceptable for routine clinical use.
There is an accompanying editorial by Neil R. Miller, MD.
Correlation Between Dry Eye and Rheumatoid Arthritis Activity
Fujita et al. evaluated the incidence of dry eye in rheumatoid arthritis (RA) patients with or without Sjögren’s syndrome (SS), and investigated the correlation between dry eye and RA activity in a prospective case-control study.
In 72 RA patients, the severity of dry eye was assessed by Schirmer test, tear break-up time, rose bengal staining and fluorescein staining. The RA activity was evaluated by the Lansbury index (LI), which is based on the duration of morning stiffness, erythrocyte sedimentation rate (ESR), grip strength and joint score. Ten percent of patients met the Japanese criteria for SS. No difference in dry eye tests or LI was observed between SS patients and non-SS patients. Even in the non-SS group, 90 percent of patients were diagnosed with probable dry eye. In SS patients, positive correlations were observed between LI and Schirmer test, ESR and Schirmer test, ESR and rose bengal staining, and grip strength and rose bengal staining. No such correlations were observed in the non-SS patients.
Dry eye is common in RA patients, including those without SS. The authors found a correlation between LI and Schirmer test in RA patients with SS, but no correlation when the entire group was analyzed. The severity of dry eye seems to be independent of RA activity.
There is an accompanying editorial by Michael A. Lemp, MD.
Multifocal ERG Changes in Patients Receiving Hydroxychloroquine
Lai et al. evaluated the longitudinal changes in multifocal electroretinography (mfERG) in patients receiving hydroxychloroquine and assessed the effects of cumulative hydroxychloroquine dose on mfERG in a prospective cohort study.
Twenty-four eyes in 12 patients receiving hydroxychloroquine underwent mfERG recordings at baseline and one to two years later. The first negative (N1) and first positive (P1) response amplitudes and peak latencies were compared with normal controls. Serial changes in the pattern of mfERG abnormalities and in response amplitudes and peak latencies were also compared between eyes in which hydroxychloroquine therapy was continued or stopped. Correlation analyses were performed to assess the effects of a cumulative dose of hydroxychloroquine on mfERG.
At baseline, reductions in N1 and P1 response amplitudes were observed in patients receiving hydroxychloroquine compared with controls. At follow-up, in addition to the reductions in N1 and P1 response amplitudes, increases in P1 peak latencies compared with controls were observed. In patients who stopped hydroxychloroquine therapy, there were significant increases in N1 and P1 response amplitudes at follow-up mfERG.
Patients receiving hydroxychloroquine showed a longitudinal decline in retinal function; patients who stopped hydroxychloroquine therapy showed improvement. Although these data are insufficient to demonstrate the sensitivity of mfERG for evaluating early hydroxychloroquine toxicity, the results suggest that serial mfERG assessment may help detect early retinal changes associated with hydroxychloroquine therapy.
There is an accompanying editorial by Michael F. Marmor, MD.
Reduced Mortality in Uveal Melanoma by Pre-Enucleation Radiotherapy
Kilic et al. studied the effect of pre-enucleation radiotherapy (PER) on melanoma-related mortality after 20 years of follow-up. In a prospective study, 167 patients with uveal melanoma were treated between 1978 and 1992 by irradiation with 8 Gy given in two fractions two days before enucleation. A group of 108 patients with uveal melanoma, treated between 1971 and 1992 by enucleation only, in the same hospital, served as a historical control group. Patients were followed up until December 2002 or death.
Melanoma-related deaths occurred in 32.3 percent of the PER-treated group and in 40.7 percent of the enucleation-only group. Mean follow-up was 9.25 years. After 48 months of follow-up a significant difference in survival became evident in favor of the PER group. The estimated 15-year survival rates for patients with melanoma in the PER group and enucleation-only group were 63.7 percent and 51.0 percent, respectively. For patients dying of all causes these percentages were 47.5 percent and 25.2 percent, respectively. In both groups, women had a better prognostic outcome than men.
The authors conclude that pre-enucleation radiotherapy (two fractions of 4 Gy) has a long-term beneficial effect on survival in patients with uveal melanoma.
Predictive Factors for Visual Acuity After Intravitreal Triamcinolone for Diabetic Macular Edema
Jonas et al. evaluated which factors may influence gain in corrected visual acuity after an intravitreal injection of triamcinolone acetonide as treatment for diffuse diabetic macular edema.
Fifty-three eyes of 43 patients with diffuse diabetic macular edema received an intravitreal injection of about 20 milligrams triamcinolone acetonide. Mean follow-up was 10.2 ± 7.6 months.
During follow-up, BCVA increased significantly (P < 0.001) by 2.8 ± 2.4 Snellen lines (–0.28 ± 0.23 logMar units). Thirty-four eyes (64 percent) had an improvement of 2 lines BCVA, and 10 (19 percent) eyes had an improvement of one line. In a multiple linear regression analysis, maximum gain in corrected visual acuity during follow-up after the intravitreal injection of triamcinolone acetonide was significantly (P < 0.001) and negatively correlated with an increased degree of macular ischemia and higher preoperative visual acuity. Improvement in BCVA was significantly and positively correlated with increased degree of macular edema (P = 0.001). Change in BCVA after the grid laser treatment prior to inclusion into the study.
The results were comparable for gain in visual acuity at six months after the injection.
The authors conclude that pronounced macular edema may have a positive impact, and marked macular ischemia and high preoperative BCVA may have a negative impact, on an increase in BCVA after an intravitreal triamcinolone injection in patients with diabetic macular edema.
Keratoconus Managed With Intacs
Good visual outcome was defined as UCVA > 20/40. The 58 eyes of the 43 patients studied were analyzed pre- and one-year post-Intacs.
Preoperative parameters were correlated simply and multiply with postoperative UCVA. Intacs were implanted in all eyes with no intraoperative complications. Six eyes underwent additional Intacs surgery. Post-Intacs, the mean ± SD UCVA improved from < 20/200 ± 0.1 line to 20/ 50-3 ± 3.1 lines, the mean ± SD BCVA was unchanged at 20/32 ± 2 lines, the mean ± SD spherical equivalent improved from -3.88 ± 1.64 to -1.04 ± 1.51 D and the mean ± SD astigmatism improved from 3.34 ± 2.23 to 1.97 ± 1.51 D.
Twenty-five eyes had a good outcome. Multiple regression analysis selected BCVA, astigmatism and spherical myopia as the preoperative predictors of outcome.
The authors conclude that Intacs improve myopia and regular astigmatism in keratoconus. Milder keratoconus (BCVA > 20/32-2 and astigmatism < 3.5 D) and significant spherical myopia (> –1.75) predict better outcome.
Roundup of Other Journals
Iris-Derived Cells Adopt Photoreceptor-Specific Phenotypes
Scientists may be one step closer in their search for possible donor cells that can be used for retinal transplantation.
Akagi et al. have demonstrated that iris cells derived from both rodents and primates can be successfully induced to adopt a photoreceptor-specific phenotype by retroviral infection in vitro. In addition, the researchers found that photoreceptor-like cells resulting from this gene therapy approach have a photoresponse to light stimuli and the potential to integrate and survive within the developing retina and demonstrate rod-opsin immunoreactivity.
To conduct this research, the investigators cultured adult rat and monkey iris tissue in serum-free medium containing basic fibroblast growth factor. Gene deliveries of Crx, Nrl, NeuroD and some combinations were performed with recombinant retrovirus.
The investigators conclude that further study of appropriate host conditions for efficient transplantation of these iris-derived cells will help shed light on their clinical application.
Erythropoietin in Proliferative Diabetic Retinopathy
Why is VEGF inhibition not sufficient to prevent retinal neovascularization in proliferative diabetic retinopathy? Watanabe et al. postulated that other “potent ischemia-induced angiogenic factors” may be involved—specifically erythropoietin.
For answers, they measured both erythropoietin and VEGF in the vitreous fluid of 144 patients using radioimmunoassay and enzyme-linked immunosorbent assay. The median vitreous erythropoietin level in 73 patients with proliferative diabetic retinopathy was significantly higher than the levels in 71 patients without diabetes.
With the use of multivariate logistic-regression analyses, the researchers found that erythropoietin and VEGF were each independently associated with proliferative diabetic retinopathy, with erythropoietin even more strongly associated than the VEGF.
From a clinical standpoint, erythropoietin blockade may be effective for the treatment of proliferative diabetic retinopathy, with erythropoietin even more strongly associated than the VEGF. From a clinical standpoint, erythropoietin blockade may be effective for the treatment of proliferative diabetic retinopathy. However, this approach could be dangerous in retinal diseases that involve apoptosis of photoreceptors, or it could worsen diabetic neuropathy if administered indiscriminately.
Roundup of Other Journals is written by Lori Baker Schena and edited by Deepak P. Edward, MD.