American Academy of Ophthalmology Web Site: www.aao.org
New Findings from Ophthalmology, AJO, and Archives
American Journal of Ophthalmology:
Roundup of Other Journals:
Treatment Alternative for Acute Primary Angle Closure
Husain et al. found that phacoemulsification and IOL implantation performed within one week of acute primary angle closure (APAC) resulted in superior IOP control, compared with laser peripheral iridotomy (LPI). However, the authors cautioned that only experienced surgeons should perform the phaco/IOL surgery given the potential for cataract surgery complications such as endophthalmitis and expulsive hemorrhage.
This randomized, controlled trial included 37 patients with cataracts who presented with APAC and who had responded to medical treatment such that IOP was less than 30 mmHg within 24 hours. The authors randomized 18 patients to LPI and 19 to phaco/IOL surgery. The primary outcome measure was failure of IOP control, which they defined as an IOP between 22 and 24 mmHg on two occasions or IOP of 25 mmHg or higher on one occasion. Over a two-year period, there were seven failures in the LPI group compared with two failures in the phaco/IOL group.
The researchers called for a larger study to look at complications.
Endothelial Cell Loss in DSAEK and Penetrating Keratoplasty
In this study, Ang et al. found that Descemet stripping automated endothelial keratoplasty (DSAEK) was superior to penetrating keratoplasty (PK) in terms of endothelial survival. More specifically, performing DSAEK resulted in a consistently lower percentage of endothelial cell loss compared with PK in the three years following surgery. These findings reinforced the authors’ preference for DSAEK as their primary procedure of choice for endothelial dysfunction.
The cohort included 206 patients (206 eyes) with Fuchs dystrophy and aphakic bullous keratopathy who were treated with similar postoperative steroid regimens at a single tertiary care center. Of these patients, 141 presented with aphakic bullous keratopathy and 65 with Fuchs dystrophy. DSAEK was performed in 119 eyes, and PK in 87 eyes. The percentage of endothelial cell loss was lower with DSAEK compared with PK at one year (30 percent vs. 37 percent), two years (36 percent vs. 45 percent), and three years (39 percent vs. 47 percent) following surgery. Graft survival was comparable between the two procedures.
SD-OCT to Diagnose Preperimetric Glaucoma
In this cohort study, Lisboa et al. demonstrated that, in the near future, spectral-domain optical coherence tomography (SD-OCT) could play an important role in the diagnostic evaluation of glaucoma suspects. They found that using SD-OCT to assess the retinal nerve fiber layer (RNFL) performed well in detecting preperimetric glaucomatous damage in eyes with suspected glaucoma. In addition, this technology performed better than topographic optic disc assessment obtained with confocal scanning laser ophthalmoscopy (CSLO).
For this investigation, the authors recruited 88 patients from the Diagnostic Innovations in Glaucoma Study: 42 patients (48 eyes) showing evidence of progressive glaucomatous change were part of the preperimetric glaucoma group; and the study’s control group included 46 patients (86 eyes) who presented without any evidence of progressive glaucomatous change. Areas under the receiver operating characteristic curves (AUCs) were calculated to summarize diagnostic accuracy of the SD-OCT and CSLO. Likelihood ratios were reported using the diagnostic categorization provided by each instrument after comparison to its normative database.
The SD-OCT parameter with the largest AUC was found to be the temporal superior RNFL thickness, followed by global RNFL thickness and temporal inferior RNFL thickness. The CSLO parameter with the largest AUC was rim area, followed by rim volume and linear cup-to-disc ratio. SD-OCT assessment of the temporal superior RNFL average thickness performed significantly better in detecting glaucomatous damage than rim area measurements from CSLO.
Abnormal results on SD-OCT (compared with the instrument’s normative database) were associated with strongly positive likelihood ratios for preperimetric glaucomatous damage.
Asymmetric Elongation of Foveal Tissue Following Macular Hole Surgery
SD-OCT allows detailed evaluation of the retina, providing researchers with insight into foveal microstructure recovery after macular hole surgery. In this study, Kim et al. used SD-OCT technology to examine the elongation profile of foveal tissue after macular hole surgery and determine its effect on visual acuity and metamorphopsia. The study revealed continuous postoperative asymmetric elongation of the foveal tissue during the first two months in all eyes—a pattern that continued six months postoperatively in a majority of eyes. This elongation was usually asymmetric, and the degree of asymmetry was associated with the amount of postoperative metamorphopsia.
This prospective, interventional case series included 31 eyes from 31 patients who underwent surgery for a macular hole less than 400 µm in diameter. The authors defined the distance between the parafoveal edge of the outer plexiform layer (OPL) as the inter-OPL distance; they measured this distance on the basis of OCT images taken at one-, two-, and six-month postoperative visits. Further elongation of the foveal tissue in certain directions was defined as asymmetric elongation. The authors also evaluated the association of the mean degree of asymmetric elongation with visual acuity and metamorphopsia.
Macular hole sealing was noted in all eyes after surgery. The horizontal inter-OPL distances measured at the three defined time points were 361.6 ± 99.6 µm, 558.8 ± 93.3 µm, and 575.4 ± 94.8 µm, respectively. The vertical inter-OPL distances were 324.2 ± 93.8 µm, 481.2 ± 104.6 µm, and 494.6 ± 85.0 µm, respectively. Both the horizontal and vertical inter-OPL distances increased during the follow-up period. Horizontal inter-OPL distances were significantly longer than vertical distances at one, two, and six months. Further nasal and superior elongation was noted on the horizontal and vertical planes in 90.3 percent and 61.3 percent of eyes, respectively.
American Journal of Ophthalmology
Increased Risk of Stroke After Retinal Artery Occlusion
Chang et al. used a population-based study in Taiwan to identify the association between retinal artery occlusion (RAO) and stroke. They found that for patients with RAO, the adjusted hazard ratio for having a stroke was 2.07 times higher than age-, sex-, and hypertension-matched controls, and 3.34 times higher in a subgroup of those 60 years and younger. Stroke incidence rate was also particularly high in the first six months after RAO.
The study cohort consisted of 464 patients with a diagnosis of RAO from January 1999 through December 2006. The control group consisted of 2,748 randomly selected patients matched with the study group by age, sex, date of index medical care, and comorbid hypertension. The investigators tracked patients from their index date for three years.
During the three-year follow-up period, 91 RAO patients (19.61 percent) and 280 controls (10.18 percent) had a stroke. Compared with the controls, the incidence rate ratios of stroke in RAO patients were 9.46 through the first month after RAO, 5.57 between one and six months after RAO, and 2.16 through three years after RAO.
Foldable Artiflex Toric Phakic Intraocular Lens
Doors et al. evaluated the short-term efficacy, predictability, stability, and safety of the foldable Artiflex toric phakic IOL (Ophtec) for the correction of myopia with astigmatism. They found that the IOL effectively and safely corrected myopia and astigmatism in the short term, with stable and predictable visual results after six months. Strict inclusion criteria, correct surgical technique, and accurate postoperative examinations were required to achieve these results. However, the authors noted that deposition of pigment and nonpigment precipitates on the IOL warrants further investigation.
This prospective, nonrandomized multicenter study included 115 eyes of 73 patients implanted with an Artiflex toric phakic IOL. Mean implanted spherical and cylindrical powers were –7.1 D and –2.14 D, respectively. Total follow-up was six months.
At six months, 99 percent of eyes had an uncorrected visual acuity (UCVA) of better than 20/40, and 81.8 percent of eyes were ±0.5 D from the intended refraction. In 74.5 percent of eyes, postoperative UCVA was equal to or better than preoperative best-corrected visual acuity (BCVA); two eyes lost two or more lines of BCVA postoperatively because of the development of synechiae. In 75.5 percent of eyes, the remaining cylinder was ±0.5 D.
There was also a significant decrease (mean, 4.8 percent) in endothelial cell density up to three months, with no additional decline between three and six months. The authors found that there were few complications, except for pigment and nonpigment precipitates (occurring in 14.8 percent and 12.2 percent of eyes, respectively, at six months). Mean misalignment was 0.6 degrees.
Retinal Function in AMD Patients After Lutein and Zeaxanthin Supplementation
Ma et al. examined the effects of lutein and zeaxanthin supplementation on retinal function using multifocal electroretinograms (mfERG) in patients with early age-related macular degeneration (AMD). They found that early functional abnormalities of the central retina could be improved by supplementation and that these improvements may be attributed to the elevations in macular pigment optical density (MPOD).
In this randomized, double-masked, placebo-controlled trial, the authors assigned 108 subjects with early AMD to the following regimens for 48 weeks: 10 mg/day of lutein (n = 27); 20 mg/day of lutein (n = 27); 10 mg/day of lutein plus 10 mg/day of zeaxanthin (n = 27); or placebo (n = 27). Thirty-six age-matched controls without AMD were also enrolled to compare baseline data with early AMD patients. mfERG responses and MPODs were recorded and analyzed at baseline and at 24 and 48 weeks.
There were significant reductions in first negative and first positive (N1P1) response densities in ring 1 to ring 3 in early AMD patients compared with the controls. Neither N1P1 response densities in ring 4 to ring 6 nor P1 peak latencies changed significantly. After eight weeks of supplementation, the N1P1 response densities showed significant increases in ring 1 for the 20-mg lutein group and for the lutein plus zeaxanthin group, and in ring 2 for the 20-mg lutein group. The increases in MPOD related positively to the increases in N1P1 response density in ring 1 and ring 2 for nearly all active treatment groups. Neither N1P1 response densities in ring 3 to ring 6 nor P1 peak latencies in all rings changed significantly in any group.
Patterns and Costs Associated With AMD Progression
Schmier et al. evaluated patterns of disease progression among individuals with age-related macular degeneration (AMD) and the costs over time. The investigators used Medicare claims data and compared costs by disease stage (dry vs. wet vs. controls). Both overall and ophthalmic average annual expenditures increased over time: The expenditures of beneficiaries with dry disease doubled over time, whereas the expenditures of those whose disease advanced to wet AMD tripled.
This retrospective data analysis used a 5 percent sample of Medicare claims data from 1997 through 2009. Beneficiaries were included if they had no diagnosis of AMD in 1997, were 65 years of age or older in 1997, had data through 2009, and had no major ophthalmic conditions. Two cohorts were identified: those who had dry AMD in 1998 and matched controls without AMD.
There were 52,607 beneficiaries who never had AMD and 1,184 who were diagnosed with dry AMD in 1998. Among beneficiaries with dry AMD, the disease progressed to the wet form by 2009 in 20.4 percent. From 1999 to 2009, average annual Medicare expenditures increased from $11,265 to $24,494 in patients whose disease did not progress, and from $11,712 to $34,308 in patients whose disease progressed. Among beneficiaries without AMD, expenditures also increased over time (from $4,736 in 1999 to $17,473 in 2009) but were consistently lower than AMD patients’ expenditures. In terms of ophthalmic expenditures, the pattern was more pronounced: Beneficiaries without AMD had annual expenditures of less than $100; beneficiaries with dry AMD had at least three times more expenditures than those without AMD; and beneficiaries with wet AMD had at least fivefold the expenditures of patients with dry disease.
The authors concluded that AMD progression is associated with increased annual Medicare expenditures. Halting or slowing disease progression using proven treatment such as AREDS-endorsed vitamins or novel technologies could have a substantial positive impact by lowering public health expenditures.
Archives of Ophthalmology
Long-Term Effects of Ranibizumab on Severity and Progression of Diabetic Retinopathy
Ip et al. evaluated the effects of intravitreal ranibizumab on the severity of diabetic retinopathy (DR) in two phase 3 clinical trials of ranibizumab for diabetic macular edema (DME). They found that ranibizumab reduced the risk of DR progression in eyes with DME. Many ranibizumab-treated eyes also experienced improvement in DR severity. Because these results are exploratory, the authors concluded that the use of intravitreal ranibizumab specifically to reduce DR progression or cause DR regression requires further study.
In this study, the authors randomized participants with DME to monthly sham, 0.3-mg ranibizumab, or 0.5-mg ranibizumab injections. Fundus photographs, taken at baseline and periodically, were graded by a central reading center; clinical examinations were performed monthly. The main outcome measures of this report were secondary and exploratory analyses. These included a two-step (or greater) and three-step (or greater) change on the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale and a composite DR progression outcome that included photographic changes and clinically important events such as occurrence of vitreous hemorrhage or need for panretinal laser.
At two years, the percentage of participants with DR progression (defined as worsening by two or more ETDRS steps or three or more ETDRS steps) was significantly reduced in ranibizumab-treated eyes compared with sham-treated eyes. In addition, DR regression (defined as improving by two or more ETDRS steps or three or more ETDRS steps) was significantly more likely in ranibizumab-treated eyes. The cumulative probability of clinical progression of DR as measured by the composite outcome at two years was 33.8 percent of sham-treated eyes compared with 11.2 percent of the 0.5-mg ranibizumab group and 11.5 percent of the 0.2-mg ranibizumab group.
Using SD-OCT to Map Distribution of Damage to the Retinal Ganglion Cell Pathway
Lee et al. examined whether automated analysis of SD-OCT can map the connectivity of the entire retinal ganglion cell body–axonal complex (RGC-AC) and found that, indeed, the amount and distribution of glaucomatous damage along the entire pathway can be quantified and charted.
They scanned 58 glaucoma patients and 58 glaucoma suspects using SD-OCT, and they performed nerve fiber layer (NFL) and optic nerve head (ONH) analysis. They determined mean regional retinal ganglion cell layer (GCL) thickness in 68 regions, NFL thickness in 120 regions, and ONH rim area in 12 wedge-shaped regions. Connectivity maps were created by identifying maximum correlations between regions’ GCL thickness, NFL thickness, and/or ONH rim area; for retinal nerve fiber bundle regions, maximum “thickness correlation paths” were also determined.
Mean regional NFL and GCL thicknesses across all macular regions were 22.5 µm and 33.9 µm, respectively, and mean regional rim area across all ONH wedge regions was 0.038 mm2. Connectivity could be mapped in all eyes of all patients; moreover, connectivity maps were easier to obtain in subjects with more glaucomatous damage.
Change in Visual Acuity and OCT Thickness After Treatment of Diabetic Macular Edema With Ranibizumab
Bressler et al. identified factors that predict the success or failure of intravitreal ranibizumab for DME in patients with visual acuity loss involving the center of the retina. The authors did not identify any baseline factors or anatomic responses during the first year of ranibizumab therapy that would preclude ranibizumab treatment for center-involved DME. They did find that baseline central subfield thickness on OCT was the strongest predictor of anatomic outcome. They also determined that reduction in central subfield thickness on OCT during the first year of treatment was associated with better visual outcomes.
The authors randomly assigned 361 eyes to intravitreal ranibizumab with prompt or deferred laser treatment within a larger trial of ranibizumab, triamcinolone acetonide, and laser treatment for DME. Among these eyes, the authors assessed baseline demographic, systemic, ocular, OCT, and photographic variables to determine any associations with change in visual acuity or central subfield thickness between baseline and one year.
After adjusting for baseline visual acuity, the authors found that better visual acuity outcomes were associated with younger age, less severe diabetic retinopathy on clinical examination, and absence of surface-wrinkling retinopathy. Reduction in central subfield thickness during the first year of treatment also predicted better visual acuity outcomes. After adjusting for baseline central subfield thickness on OCT, the presence of hard exudates was associated with more favorable improvement on OCT.
Ophthalmology summaries are written by Lori Baker Schena, EdD. American Journal of Ophthalmology summaries are edited by Thomas J. Liesegang, MD. Archives of Ophthalmology summaries are written by Amitha Domalpally, MD.
Roundup of Other Journals
New Findings in Leber Congenital Amaurosis
Two articles published by Nature Genetics shed new light on Leber congenital amaurosis (LCA), a typically autosomal recessive condition in which 70 percent of cases are caused by mutations in 16 genes—all of which are linked to various retinal functions.
In a “Letters” article, Koenekoop et al. pinpointed a new disease mechanism underlying LCA. Looking at eight families with the condition, the researchers used exome sequencing to identify mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 that encodes nicotinamide mononucleotide adenylyltransferase 1. They found that all the family members with NMNAT1 mutations also had macular colobomas, areas of severe foveal degeneration in which tissue and photoreceptors are lacking. Specifically, the researchers demonstrated that mutations reduced the enzymatic activity of NMNAT1 in NAD biosynthesis and affected protein folding. These findings offer the first link between endogenous NMNAT1 and a human nervous system disorder.
In a “Brief Communications” article, Perrault et al. presented findings that suggest NMNAT1 mutations affect neuroprotection of photoreceptor cells; the researchers hypothesize that one of the mechanisms underlying LCA is the inability to protect against neuronal degeneration. They found that in 22 unrelated individuals, compound heterozygous and homozygous NMNAT1 mutations were responsible for severe neonatal neurodegeneration of the central retina and early-onset atrophy. In addition, their clinical presentation was consistent with LCA. The authors concluded that the presence of pathogenic or recurrent NMNAT1 mutations in individuals with LCA—in contrast to individuals without the disease—provides strong evidence that these mutations actually cause the disease.
Comparing Results From Penetrating Keratoplasty and Deep Anterior Lamellar Keratoplasty
Sögütlü Sari et al. examined eyes with moderate to advanced keratoconus and found that results from deep anterior lamellar keratoplasty (DALK) using the big-bubble technique are comparable to those from penetrating keratoplasty (PK).
In this prospective, randomized case study, the authors included 174 eyes of 140 consecutive patients with moderate to advanced keratoconus. Of these eyes, 99 underwent DALK with the big-bubble technique, and 75 underwent PK. Main outcome measures were intraoperative and postoperative complications, UCVA, best-corrected visual acuity, refraction, topographic astigmatism, contrast sensitivity function (CSF), and ocular higher-order aberration (HOA). The two procedures demonstrated comparable results in the parameters of VA, refraction, CSF, and HOA.
In light of these findings, the authors concluded that DALK represents a viable treatment alternative for such patients.
Implanting Trabecular Micro-Bypass Stents During Cataract Surgery
Craven et al. found that implanting an iStent trabecular micro-bypass stent (Glaukos) during cataract surgery provides significantly better control of IOP compared with cataract surgery alone in patients with mild to moderate open-angle glaucoma. In addition, the long-term safety profile was similar between the two groups.
In this multicenter clinical trial, the authors randomly assigned eyes with mild to moderate glaucoma and an unmedicated IOP between 22 mmHg and 36 mmHg to have cataract surgery with stent implantation or cataract surgery alone. Patients were followed for 24 months postoperatively.
At 24 months, a higher proportion of patients in the stent group attained an IOP of 21 mmHg or lower without ocular hypotensive medications compared with the patients who underwent only cataract surgery. In addition, the mean IOP remained stable in the stent group between 12 and 24 months, but IOP increased in the group of patients who underwent only cataract surgery.
The authors concluded that in terms of managing IOP, a single trabecular micro-bypass stent implanted during cataract surgery might be an option in patients with cataract and mild to moderate glaucoma.
Roundup of Other Journals is written by Lori Baker Schena, EdD, and edited by Deepak P. Edward, MD.