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January’s American Journal of Ophthalmology:
December’s American Journal of Ophthalmology:
November’s Archives of Ophthalmology:
October’s Archives of Ophthalmology:
Roundup of Other Journals:
Rituximab to Treat Thyroid-Associated Ophthalmopathy
A retrospective, interventional case series by Chong et al. demonstrates a clinical benefit of anti-CD20 (rituximab) in the treatment of severe thyroid-associated ophthalmopathy that is refractory to corticosteroid therapy or orbital decompression.
Thyroid-associated ophthalmopathy affects 30 to 50 percent of patients with Graves’ disease. It is thought that B cells may produce autoantibodies against thyroid-stimulating hormone receptors and insulinlike growth factor-1 receptors. Rituximab depletes B cells by enhancing apoptosis and promoting antibody-dependent cellular toxicity and complement-dependent cellular toxicity. In the six patients studied, four developed dysthyroid optic neuropathy prior to the rituximab treatment. Orbital inflammation and dysthyroid optic neuropathy improved following rituximab treatment in all six patients. No one experienced disease relapse, and proptosis remained stable.
While the authors urge caution due to the uncontrolled nature of the study, they assert these data justify conducting prospective studies to determine whether rituximab is a viable alternative in patients with progressive, corticosteroid-resistant thyroid-associated ophthalmopathy.
27-Gauge System for Vitrectomy
Oshima et al. have developed a 27-gauge instrument system for transconjunctival microincision vitrectomy surgery that includes an infusion line, high-speed vitreous cutter, illumination system and a variety of vitreoretinal instruments such as membrane forceps and sharp-tipped endophotocoagulation probes.
They utilized this system in an experimental, interventional case series of 31 eyes of 31 patients. The investigators found the performance of the 27-gauge vitreous cutter was not yet adequate for treating complex proliferative vitreoretinal pathologies. However, the 27-gauge system proved adequate for treating eyes with a macular hole, epiretinal membrane, macular edema, macular traction syndromes, simple vitreous hemorrhage, focal traction retinal detachment and vitreous biopsy for cytological diagnosis. No eyes in this series needed conversion to large-gauge instrumentation, and all sclerotomies self-sealed without hypotony from day one.
The investigators conclude that this study confirms the preliminary safety and practicality of the 27-gauge system in selected cases but that it needs further refinement to treat the full range of vitreoretinal diseases.
Definitions of Success in Glaucoma Surgery Vary Widely
Intraocular pressure constitutes the most frequently used measure of success in glaucoma surgery studies. Yet how consistent is this measurement among the various studies focusing on surgical intervention to reduce IOP?
According to Rotchford and King, it is not consistent at all. The researchers conducted a search on PubMed using the term “trabeculectomy” in publications over the past five years. They identified 92 distinct IOP-related definitions of success from the 100 publications meeting the inclusion criteria. They then applied each IOP-related definition of success to a group of 100 patients who had undergone trabeculectomy. Using the 92 distinct definitions, the researchers found that success rates for these trabeculectomies ranged from 36 percent for the strictest definition to 98 percent for the most liberal.
The authors note that meaningful comparison between different studies is difficult when the definitions of success are so different.
Anisometropia in Hispanic and African-American Children
Borchert et al. conducted a population- based cross-sectional study on 3,030 Hispanic and 2,994 African-American children aged 6 to 72 months from Southern California to determine anisometropia prevalence and associated risk factors.
The authors found that spherical-equivalent and cylindrical anisome-tropia greater than 1 D each affects 4 to 6 percent of Hispanic and African-American children. Except for cylinder axis vector, the prevalence of anisometropia did not diminish beyond one year of age. Anisometropia of greater than 3 D was rare, only affecting 0.4 percent of children in both ethnic groups. In addition, the association of biological and environmental risk factors with anisometropia was lacking in these populations. Cylindrical an-isometropia decreased by age 1 in both ethnic groups.
According to the authors, since the prevalence of anisometropia is relatively stable between 1 and 6 years of age, screening programs for anisometropia could be conducted any time in this age group.
Tracking Progression of Glaucomatous Field Defects
Heijl et al. used data from the Early Manifest Glaucoma Trial (EMGT) to describe the progression of glaucomatous field defects in high-tension glaucoma, normal-tension glaucoma and pseudoexfoliation glaucoma.
After a six-year follow-up, 80 of the 118 participants had shown definite visual field progression. The researchers found large interpatient variability in the rate of progression—not only among the three diagnostic groups but also within the groups, thus making it difficult to predict individual progression rates.
Many of the untreated EMGT patients progressed slowly, resulting in a median progression rate of 70 years for the total patient group going from a full field to blindness. However, a large number of patients progressed much more rapidly, especially the pseudoexfoliation patients, which made the mean progression rate for the total patient group about 25 years from a full field to blindness.
Prospective Study of DMEK
Price et al. conducted a prospective study of Descemet’s membrane endothelial keratoplasty (DMEK), an alternative to Descemet’s stripping automated endothelial keratoplasty (DSAEK).
In this multicenter study, 60 eyes of 56 consecutive patients with Fuchs’ endothelial dystrophy, pseudophakic bullous keratopathy or failed previous graft underwent DMEK. At one month, 20 percent of the DMEK eyes had 20/20 vision, 31 percent were 20/25 or better and 84 percent were 20/40 or better. At three months, 26 percent had 20/20 vision, 63 percent were 20/25 or better and 94 percent were 20/40 or better (excluding four eyes with advanced ocular comorbidity).
According to the authors, these three-month rates of 20/20 and 20/25 vision exceeded the best rates reported with DSAEK at six months with comparable endothelial cell loss. However, donor preparation and attachment are more challenging with DMEK than with DSAEK.
Improving Patient Adherence to Glaucoma Medications
Okeke et al. used a multifaceted intervention strategy to improve adherence in patients using daily topical eyedrops for glaucoma. While this approach significantly increased patient compliance, the researchers could not determine which aspects of the intervention were most valuable and which parts could be realistically implemented in a clinical practice.
This study involved 66 patients who were being treated with a prostaglandin analog and, during an initial three-month period, had been taking 75 percent or fewer of their doses. They were randomized into two groups. The intervention group watched an educational video, reviewed barriers to drop taking and discussed possible solutions with a study coordinator. They also received regular phone reminders and had audible and visible reminders activated on their dosing aid devices. The control group did not receive any intervention except dosing instructions. The intervention group improved their adherence rate from 54 to 73 percent. The mean adherence rate of 46 percent remained statistically unchanged in the nonintervention group.
Effect of Statins on AMD
Data from the Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) do not support a large effect of statins in decreasing the risk of developing advanced age-related macular degeneration among patients with bilateral drusen.
For this study, Maguire et al. used data from CAPT, which involved participants with large bilateral drusen and visual acuity of greater than 20/40 in each eye. Of the 744 CAPT patients who completed an interview about medications, 39.8 percent reported statin use. Among the 744 patients, advanced AMD developed in 332 eyes of 242 patients, choroidal neovascularization in 222 eyes of 176 patients and geographic atrophy in 114 eyes of 80 patients. With adjustment for other risk factors, the estimated risk ratio for eyes associated with statin use was 1.15 for advanced AMD, 1.35 for choroidal neovascularization and 0.80 for geographic atrophy.
While a randomized clinical trial could address the impact of statin use on AMD, the logistics of that study—given the number of older people already on statins—would make this effort difficult.
American Journal of Ophthalmology
Sub-Tenon’s Triamcinolone Acetonide Injections for Scleritis
The role of corticosteroid injections around the eye in the treatment of scleritis is a controversial topic. Johnson and Chu investigated sub-Tenon’s triamcinolone acetonide injections in patients with scleritis in a retrospective, interventional case series.
A chart review was conducted of all patients receiving sub-Tenon’s triamcinolone injections for scleritis between August 2001 and August 2007. Outcome measures included subjective improvement, presence of inflammation and adverse events.
Eleven patients (12 eyes) were included. The mean age was 50 years; two patients were male and nine female. Six patients had systemic autoimmune disease. All patients were receiving systemic medications for scleritis at the time of injection. Mean initial follow-up time was three weeks. Ten of 11 patients reported subjective improvement and 10 patients had objective improvement in inflammation. Three patients had side effects, including ocular hypertension, worsening of cataract and subconjunctival hemorrhage with periorbital ecchymosis.
This small pilot series suggests that sub-Tenon’s triamcinolone injections may be a useful adjunct to achieving transient, partial improvement of subjective pain and objective inflammation in patients with scleritis that are awaiting systemic medications to take effect. Adverse events were manageable in this small series.
Sequential Glaucoma Implants in Refractory Glaucoma
Patients refractory to treatment following an implant are a nemesis for the glaucoma specialist. Anand et al. evaluated the efficacy of a second glaucoma implant in eyes with prior implant surgery and inadequate IOP control in a cohort study.
Patients undergoing a second glaucoma implant surgery from 1996 to 2008 were included. Success was defined as IOP of less than 21 mmHg (criterion one) and IOP of less than 17 mmHg (criterion two), with at least 25 percent reduction in IOP and no prolonged hypotony.
Forty-three eyes (43 patients) had a mean follow-up of 32.6 months. Using criterion one, life-table analysis demonstrated success rates at one, two and three years of 93, 89 and 83 percent, respectively. Using criterion two, success rates were 83, 75 and 75 percent, respectively. At last follow-up, mean IOP and mean number of medications were lower following the second implant. There was no difference between preoperative and most recent logMAR visual acuities. The most frequently used second implants (Baerveldt implant and Ahmed valve) were similar in percentage of IOP reduction.
Incidence and Factors Related to Macular Hole Reopening
The reason for reopening of macular holes remains unknown. In a retrospective, comparative, consecutive case series, Kumagai et al. investigated the incidence and the factors that can cause a reopening of a macular hole (MH) after a surgical closure.
The medical charts of all patients who underwent vitrectomy with or without internal limiting membrane peeling for an idiopathic full-thickness MH were reviewed. In all cases, the MH was closed successfully. Simultaneous phacoemulsification with IOL implantation was performed on all phakic patients who were older than 40 years.
The authors studied 877 eyes of 831 patients with a mean age of 64.9 years. Combined cataract extraction with vitrectomy was performed on 763 eyes of 775 phakic eyes. The mean follow-up time after MH surgery was 57.7 months. Two groups were studied: an ILM-off group and an ILM-on group. The MH reopened in two eyes (0.39 percent) in the ILM-off group and in 26 eyes (7.2 percent) in the ILM-on group. Factors related to the reopening in the ILM-on group were refractive error and intraoperative peripheral tear formation.
The authors conclude that ILM peeling significantly decreases the incidence of the reopening of an MH and that myopia and intraoperative retinal tears may be related to the reopening.
Excess Lead in the Neural Retina in AMD
Accumulated lead and cadmium exposure is associated with some systemic diseases of aging. Lead and cadmium can promote diseases of aging by increasing oxidative stress and by producing inflammatory cytokines. Erie et al. measured lead and cadmium in retinal tissues of human donor eyes with and without age-related macular degeneration.
The authors determined lead and cadmium concentrations in retinal tissues (neural retina and retinal pigment epithelium–choroid complex) in 25 subjects with AMD (50 donor eyes) and 36 normal subjects (72 donor eyes) by using inductively coupled plasma-mass spectrometry. Severity of AMD was graded by using color fundus photographs.
The neural retinas of subjects with AMD had increased lead concentrations compared with normal subjects. There was no difference in lead concentration in the retinal pigment epithelium–choroid complex among subjects with AMD and those with normal eyes. Cadmium concentration in the neural retina and retinal pigment epithelium–choroid complex in subjects with AMD was not different from concentrations in subjects with normal eyes.
Bevacizumab vs. Ranibizumab for AMD
Subramanian et al. report the outcomes of a controlled trial comparing bevacizumab with ranibizumab for the treatment of age-related macular degeneration.
In a single-center clinical trial, patients who met inclusion criteria were randomized 2-to-1 to bevacizumab or ranibizumab. Each patient volunteered to have one eye treated. Patients were given either bevacizumab or ranibizumab every month for the first three months, followed by an optical coherence tomography–guided, variable-dosing schedule. Main outcomes measured were visual acuity and foveal thickness.
Twenty patients completed the six-month follow-up. Thirteen patients received bevacizumab and seven patients received ranibizumab. No subjects in either group lost more than 15 letters. The average preoperative visual acuity was 31.6 letters in the bevacizumab group and 30.4 letters in the ranibiz-umab group. At the six-month follow-up, mean vision was 46.4 letters in the bevacizumab group and 37.4 letters in the ranibizumab group. Two-tailed tests failed to show statistical significance between the two groups. Patients in the bevacizumab group underwent an average of five injections, while patients in the ranibizumab group underwent a mean of four injections.
As this study conveys results of a small number of patients, further studies with larger sample sizes are needed in order to establish statistical significance.
Complications Arising From DSAEK
Descemet’s stripping automated endothelial keratoplasty (DSAEK) is a frequent alternative now to penetrating keratoplasty. Shih et al. examined the complications encountered after DSAEK at one institution in a retrospective case review.
The first 126 consecutive DSAEKs done at the New York Eye & Ear Infirmary from March 2006 to March 2008 were reviewed. A total of 126 eyes of 113 patients underwent DSAEK. All cases were included regardless of outcome. All complications intraoperatively and postoperatively were recorded.
Graft detachment was the most common complication, occurring in 22 eyes; 17 of these were successfully repositioned. Idiopathic graft failure occurred in 15 eyes. Other visually significant complications included graft rejection (two eyes), choroidal effusion (two eyes), epithelial ingrowth (two eyes), endophthalmitis (one eye), pupillary block (one eye) and suture abscess (one eye). Twenty-four eyes had nonvisually significant complications, including decentered lenticles, interface fibers, partial peripheral detachments, retained Descemet’s membrane and eccentric trephination.
While DSAEK is a viable alternative to penetrating keratoplasty, serious complications may still occur postoperatively. While certain rare complications like endophthalmitis, epithelial ingrowth and suture abscess may affect vision, more common complications such as decentered lenticles and partial peripheral detachments are less likely to affect visual outcome.
Archives of Ophthalmology
Cell Loss After Excimer Laser Keratorefractive Surgery
Patel and Bourne examined changes in endothelial cell density and measured the rate of endothelial cell loss in the same eyes before and nine years after LASIK or photorefractive keratectomy.
Twenty-nine eyes (16 patients) had myopic LASIK or PRK. Endothelial photographs were obtained before and nine years after surgery. None of the eyes were treated with a femtosecond laser or with mitomycin-C. Endothelial cell loss was 5.3 percent over the nine-year study period. However, the average annual rate of endothelial cell loss was 0.6 percent, which was the same rate as in 42 normal corneas that had not had surgery. Endothelial cell loss was unrelated to the depth of ablation or residual bed thickness.
The authors conclude that the annual rate of endothelial cell loss after excimer keratorefractive surgery (without mitomycin-C) is not different from the physiologic age-related rate of cell loss in normal corneas. Given the popularity of refractive surgery, the results of this study are important because they support the use of corneas that have had excimer ablation as donors for posterior lamellar keratoplasty.
Prediction of Proliferative Diabetic Retinopathy by Hemoglobin Level
Conway et al. examined the relationship of total hemoglobin level with the incidence of proliferative diabetic retinopathy in 426 individuals (213 men, 213 women) with childhood- onset type 1 diabetes.
The 426 individuals were free of PDR at baseline biennially for up to 18 years. PDR was determined by stereo fundus photography. Analyses were conducted sex specifically using Cox proportion hazards modeling.
Hemoglobin levels ranged from 9.2 to 20 g/dl, with a mean of 16.2 g/dl in males and 14.1 g/dl in females. During the follow-up period, 48 percent of the population developed PDR. Although the incidence was equal in both genders (103 events in males, 103 events in females), higher hemoglobin levels exhibited a direct relationship with the incidence of PDR in males and a U-shaped (quadratic) relationship in females. Hemoglobin was also predictive of macular edema and two-step progression of retinopathy in both genders.
The authors conclude that high levels of hemoglobin predict the progression of retinopathy and the incidence of macula edema and PDR in type 1 diabetes—although in females, the risk of PDR is increased at both ends of the hemoglobin range.
Risk Factors for Normal-Tension Glaucoma
Kee et al. searched risk factors for normal-tension glaucoma among subgroups of patients. In 93 patients with unilateral normal-tension glaucoma, the authors performed intereye comparison of baseline spherical equivalent, central corneal thickness, untreated IOP, disc area and zone beta variables among the following four subgroups: subgroup 1 (50 years of age and younger and visual field pattern standard deviations less than or equal to 8 dB), subgroup 2 (50 years of age and younger and deviations greater than 8 dB), subgroup 3 (older than 50 and deviations less than or equal to 8 dB) and subgroup 4 (older than 50 and deviations greater than 8 dB).
The authors included 14, 27, 30 and 22 patients in subgroups 1, 2, 3 and 4, respectively. The untreated IOP in subgroup 1, the zone beta variables in subgroup 2 and both the untreated IOP and the zone beta variables in subgroups 3 and 4 were significantly greater in the eyes with glaucoma than in the normal contralateral eyes. The other variables showed no significant difference between the eyes in any subgroup.
The authors conclude that zone beta variables (and not the untreated IOP) may represent significant risk factors in young patients having normal-tension glaucoma with moderate to severe visual field loss.
Features and Function in Multiple Evanescent White Dot Syndrome
Hangai et al. conducted a case-series study to examine retinal features and retinal function of eyes with multiple evanescent white dot syndrome (MEWDS) by using spectral-domain optical coherence tomography and microperimeter-1.
The authors used speckle-noise-reduced SD-OCT to compare characteristic MEWDS lesions (hypofluorescent in the late-phase of indocyanine green angiography) among five eyes of five patients with MEWDS. Three patients were examined weekly by using SD-OCT and microperimeter-1 until the signs and symptoms of MEWDS resolved.
During diagnosis, the SD-OCT images revealed moderately reflective focal lesions in the outer photoreceptor layer, within the areas where the inner/outer segment junction was disrupted. This unique feature corresponded with the hypofluorescent spots observed on late-phase indocyanine green angiography images.
Enhanced SD-OCT and microperimeter- 1 revealed a shift in the areas of inner/outer segment junction disruption and reduced retinal sensitivity from the area surrounding the optic disc to the temporal macula. The disruption of the inner/outer segment junction was corrected and the retinal sensitivity was normalized in all eyes in approximately one month from the diagnosis of MEWDS.
The authors conclude that enhanced SD-OCT revealed abnormalities in the photoreceptor layer that were specific to MEWDS and that seemed to change location during clinical recovery from MEWDS.
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
Incidence of Cataract in Diabetes Patients
Published online Sept. 17, 2009
In a population-based cohort study of Danish patients with type 1 diabetes, Grauslund et al. found a high 25-year incidence of cataract. The original cohort of patients with type 1 diabetes was first identified in 1973, with diabetes markers such as diabetic retinopathy measured in 573 patients in 1981–1982. This cohort was followed until January 2006.
The mortality-adjusted incidence of cataract was 29.4 percent. The median age at the time of surgery was 59.3 years and the median duration of type 1 diabetes was 42 years. According to the authors, cataract surgery was performed approximately 20 years earlier in this diabetic population than among nondiabetic individuals from the Blue Mountains Eye Study—an observation not previously reported in the literature.
The only risk factors that were statistically significant predictors of cataract were age and maculopathy at baseline. Gender, glycemic regulation, proteinuria, smoking, blood pressure and level of retinopathy were unrelated to cataractogenesis.
The researchers conclude that since the link between maculopathy and cataract constitutes a new finding, this association should be the focus of future studies.
In the meantime, patients with long-term type 1 diabetes are advised to undergo regular lens exams.
Canadian Medical Students Report Gaps in Ophthalmology Training
Canadian Journal of Ophthalmology
A survey of first-year residents who had graduated from medical schools in Canada indicates that most medical students are not entering their residency possessing confidence with their ophthalmology knowledge and skill set. Noble et al. designed the survey to compare undergraduate ophthalmology education in Canada to guidelines set forth by the International Council of Ophthalmology (ICO), which outlined the core competencies medical students should complete to become primary care physicians capable of addressing ophthalmic pathologies.
Of the 386 out of 1,425 residents who responded to the survey, a majority (64 percent) stated that they had “too little” or “no exposure” to ophthalmology in their medical school curriculum. A majority (76.2 percent) of respondents also stated that they had received one week or less of overall exposure to ophthalmology. While 81.8 percent said they had sufficient exposure to lens/cataract and 81.6 percent to corneal/external disease, only 41.9 percent said they received adequate time allocation to vitreoretinal disease.
The authors call for development of a national standardized curriculum based on the ICO guidelines to ensure that the next generation of Canadian physicians are confident in their ability to manage patients with vision problems.
Ophthalmology Residents in Canada Satisfied With Training Programs
Canadian Journal of Ophthalmology
Zhou et al. have found that Canadian ophthalmology residents report high levels of satisfaction with their training programs and that these programs are effective in meeting most of the core learning objectives set forth by the International Council of Ophthalmology (ICO). Of the 99 residents contacted to take the cross-sectional, Web-based survey, 40 responded (26 current residents and 14 graduates).
Eighty-five percent of the respondents expressed satisfaction with their residency program. The residents rated their clinic-based training as satisfactory, yet noted they received insufficient exposure to low vision rehabilitation, refraction and glasses prescription, and neuro-ophthalmology. These residents were also satisfied with their surgical training, with more than 60 percent rating case volume, complexity and variety as satisfactory or better.
However, they reported insufficient exposure to extracapsular cataract extraction, refractive surgery and orbital surgery. While all the graduates surveyed passed their Royal College licensing examinations on their first try, they did respond that their training in such nonclinical areas as practice management, and staffing and administration skills was insufficient.
The authors conclude that while residents appear satisfied with their training, there is room for improvement in certain areas of the residency curriculum.
Determining Optimum Set of IOLs Needed for Humanitarian Missions
Journal of Cataract and Refractive Surgery
One of the challenges of preparing for a humanitarian mission to perform cataract surgery in developing nations is the need to order a set of IOLs that covers a wide enough range of powers to achieve emmetropia.
This study by Lombard et al. describes a strategy to calculate the optimal set of IOLs to order for a specific humanitarian mission, allowing planners to minimize the number of unused IOLs and reduce the chance that any patient will be rejected for cataract surgery because an appropriate IOL power is not available.
The spreadsheet-based model, based on data from 103 patients, was designed to predict the IOL distribution, range and powers for a given number of planned cataract operations. The authors used statistical modeling to ensure patients received an acceptable postoperative refraction. The authors’ model predicted that more than 98 percent of all patients would have access to IOLs within +1 D above and +0.5 D below the calculated power for emmetropia.
They conclude that while this model requires validation with data from future missions, it has the potential to limit the number of excess IOLs in a cost-effective manner.
Roundup of Other Journals is written by Lori Baker Schena and edited by Deepak P. Edward, MD.