American Academy of Ophthalmology Web Site: www.aao.org
New Findings from Ophthalmology, AJO and Archives
May’s American Journal of Ophthalmology:
March’s Archives of Ophthalmology:
Roundup of Other Journals:
Results from a placebo-controlled trial reported by Christen et al. of seemingly healthy female health professionals indicate that alternate-day treatment with 600 IU of natural-source vitamin E has no beneficial effect on age-related cataract or cataract subtypes.
The trial involved 39,876 women aged 45 years or older randomly assigned to receive either 600 IU of natural source vitamin E or placebo on alternate days for 9.7 years. The researchers found no significant difference between the vitamin E and placebo groups in the incidence of cataract (1,159 cases vs. 1,217 cases, respectively). In addition, no differences between the groups were seen concerning the incidence of nuclear, cortical or posterior subcapsular cataract. The data also indicated no statistically significant beneficial or harmful effect of vitamin E on cataract extraction.
The authors note that ongoing trials are currently under way to determine whether long-term treatment with other antioxidant nutrients, or various combinations of nutrients, can perhaps delay cataract onset or progression.
An analysis of randomized controlled trials (RCTs) by Li et al. supports the theory that a major factor in preventing posterior capsular opacification after cataract surgery is an IOL with a sharp-edged design.
The researchers conducted a comprehensive literature search using the Cochrane Collaboration methodology to identify RCTs. They included 10 RCTs involving 1,202 eyes with senile cataract, focusing on the effect of Alcon’s AcrySof IOLs on the development of PCO compared with silicone or PMMA IOLs. They found that AcrySof had a lower PCO score than round-edged silicone. In addition, both sharp-edged AcrySof and sharp-edged silicone IOLs had a significantly lower Nd:YAG capsulotomy rate than that of round-edged silicone or PMMA IOLs.
Price and Price conducted a retrospective analysis to identify the factors that correlate with higher postoperative endothelial cell density and reduced postoperative cell loss. In addition, they tracked the rate of endothelial cell loss for a two-year period after Descemet’s stripping endothelial keratoplasty (DSEK).
They identified three surgical factors that significantly influenced endothelial cell loss six months after DSEK: the type of graft-insertion forceps, whether the procedure was combined or stand-alone and use of a graft-reattachment procedure.
Specifically, the use of single-point fixation forceps for graft insertion resulted in significantly less postoperative cell loss.
The cell loss was also less in grafts that did not require repositioning and when DSEK was performed as a combined procedure. While the cell loss with DSEK was higher than experienced in a separate penetrating keratoplasty series at the researchers’ center, it was consistent with more donor tissue manipulation in DSEK.
In a subset of patients with a lamellar macular hole who have progressed to significant levels of central vision disturbance, vitrectomy with internal limiting membrane stripping appears to be a beneficial treatment approach.
This case series by Garretson et al. involved 27 eyes of 27 patients with a lamellar macular hole and central vision loss who underwent three-port vitrectomy with ILM stripping. Visual acuity improved in 25 of 27 eyes (93 percent) following the procedure, with a mean improvement of 3.2 Snellen lines.
In addition, optical coherence tomography, which was completed in 24 of 27 patients (89 percent), appeared to show postoperative improvement—approaching a more normal morphologic appearance—in the vast majority of patients. With the advent of OCT, diagnosis of a lamellar macular hole can now be based on both clinical examination and OCT findings.
The researchers conclude that vitrectomy with ILM peeling may be an appropriate and viable treatment option for lamellar macular hole patients with central vision loss.
American Journal of Ophthalmology
Schadlu et al. investigated the role of intravitreal bevacizumab in individuals with choroidal neovascularization resulting from ocular histoplasmosis syndrome.
In a chart review of 28 eyes of 28 patients with CNV secondary to ocular histoplasmosis syndrome, the average pretreatment logMAR visual acuity was 0.65 (Snellen equivalent of 20/88). With a mean follow-up of 22 weeks and with an average of 1.8 intravitreal injections, the average final logMAR visual acuity was 0.43 (Snellen equivalent of 20/54). Twenty eyes (71 percent) experienced an increase in central visual acuity, whereas four eyes (14 percent) were unchanged and four eyes (14 percent) experienced a decrease in vision.
The authors conclude that intravitreal bevacizumab improved or stabilized visual acuity in about 86 percent of patients with neovascular complications of ocular histoplasmosis syndrome.
Tzelikis et al. investigated whether implantation of an IOL with a modified anterior aspheric surface resulted in reduced spherical aberration and improved contrast sensitivity after cataract surgery.
In this case control study of 25 patients with bilateral cataract, the Tecnis Z9001 (AMO), an IOL with a modified anterior surface, was compared with the ClariFlex (AMO), a biconvex lens with spherical surfaces. Ocular aberrations for 5-mm and 6-mm pupils were measured with a Hartmann-Shack aberrometer. Quality of vision was measured by visual acuity and contrast sensitivity over a three-month period.
The investigators found no statistically significant difference in postoperative uncorrected- and best-corrected visual acuity after a follow-up of three months. Postoperative contrast-sensitivity testing revealed significant differences favoring the Tecnis lens under photopic and mesopic conditions. These differences reached statistical significance under photopic conditions at three spatial frequencies and under mesopic conditions at all spatial frequencies. When analyzing higher-order aberrations, the difference between the lenses was statistically significant at the 5-mm and 6-mm pupil diameters, with the Tecnis lens inducing less higher-order aberration and also less spherical aberration than the ClariFlex lens.
Shimura et al. compared the effect of an intravitreal injection of bevacizumab with that of triamcinolone acetonide for reduction of diabetic macular edema.
Twenty-eight eyes of 14 patients with bilateral DME participated in this study. One eye of each patient received a 4-mg intravitreal injection of triamcinolone acetonide and the other eye received a 1.25-mg intravitreal injection of bevacizumab. The clinical course of BCVA with a logMAR chart and averaged foveal thickness using optical coherence tomography was monitored for up to 24 weeks after the injection.
Before the injection, average foveal thickness and visual acuity were 522 µm and 0.64 in the triamcinolone-injected eyes and 527 µm and 0.61 in the bevacizumab-injected eyes, respectively. One week after the injection, both eyes showed significant regression of macular edema. The triamcinolone-injected eyes (342 µm and 0.33) showed significantly better improvement than the bevacizumab-injected eyes (397 µm and 0.37). Both sets of eyes, however, showed recurrence of macular edema with time, even at 24 weeks. Triamcinolone (410 µm and 0.47) maintained better improvement than bevacizumab (501 µm and 0.61).
Intravitreal injection of triamcinolone acetonide showed better results in reducing DME and in improving vision than did bevacizumab. This finding suggests that the pathogenesis of DME is not only attributable to VEGF dependency but also to other mechanisms suppressed by corticosteroids.
Randleman et al. evaluated the ectasia risk score system for identifying patients at high risk for developing ectasia after LASIK.
Fifty eyes that developed ectasia and 50 control eyes with normal postoperative courses after LASIK were analyzed and compared using a score system that assigns points to the following variables: topographic pattern, predicted residual stromal bed thickness, age, preoperative corneal thickness and manifest refraction spherical equivalent.
In this study, 92 percent of eyes with ectasia were correctly classified as being at high risk for the development of ectasia, while 6 percent of controls were incorrectly classified as being at high risk for ectasia. Significantly more eyes were classified as high risk by the ectasia risk score than by traditional screening parameters relying on abnormal topography or residual bed stromal thickness of less than 250 µm. There was no difference in the sensitivity or specificity of the ectasia risk score system in the population from which it was derived and this independent population of ectasia cases and controls.
Archives of Ophthalmology
Lau et al. have undertaken an open-label trial to determine the voriconazole levels obtained in human aqueous humor after administration of a 1 percent solution preserved with 0.01 percent benzalkonium chloride. Levels were checked either every six hours for three days or hourly for four doses.
Ten participants were selected among patients scheduled to undergo elective anterior segment surgery, and aqueous humor samples were tested using liquid chromatography. Results were compared with minimum inhibitory concentration levels for common fungal pathogens. The mean voriconazole concentration after hourly dosing was 1.9 µg/ml and after a single dosing every six hours was 0.94 µg/ml.
The authors conclude that voriconazole eyedrops penetrate well into human aqueous humor and, as such, would be effective in treating keratitis caused by infection with Candida and Aspergillus.
Tanihara et al. investigated the effects and safety of the topical administration of an ophthalmic solution of a selective Rho-associated coiled coil-forming protein kinase (ROCK) inhibitor, SNJ-1656, in healthy male adult volunteers.
The researchers conducted two trials. In the single-instillation trial, 45 volunteers were randomly subdivided into five groups and treated with SNJ-1656 in concentrations of 0.003 percent, 0.01 percent, 0.03 percent, 0.05 percent and 0.1 percent in stepwise fashion. In the repeated-instillation trial, 36 volunteers were assigned to receive SNJ-1656 ophthalmic solution at the following concentrations and dosages: 0.05 percent once daily, 0.1 percent once daily, 0.05 percent twice daily or 0.1 percent twice daily.
In the single-instillation study with 0.1 percent SNJ-1656, there was a maximal IOP change of 3 ± 1.16 mmHg from baseline, and it was observed at four hours after instillation. This number was larger than the reductions after instillation of lower concentrations (0.003 to 0.05 percent) of SNJ-1656.
In the repeated-instillation study, the IOP-lowering effects of SNJ-1656 on the seventh day were similar to those on the first day in once- or twice-daily administration. The maximal changes in IOP in the SNJ-1656 groups were observed from two to four hours after instillation.
On slit-lamp examination during the trial, there were no significant adverse findings except conjunctival hyperemia after instillation.
Wu et al. studied 4,092 participants between the ages of 40 and 84 in the Barbados Eye Studies, which assessed a predominantly black population with ancestry similar to African-Americans. Height, weight and blood pressures were recorded, and eye photographs and various ocular measurements were taken. Participants with specific findings were also referred for a comprehensive ophthalmologic exam.
At the beginning of the study from 1987 to 1992, 300 participants had glaucoma, including 141 who had been diagnosed and treated. After nine years of follow-up, 764 (19 percent) of the participants had died. After adjusting for other factors, the researchers found that glaucoma was not associated with the risk of death overall. However, the risk of death from cardiovascular diseases tended to be higher (38 percent) in individuals with a previous diagnosis or treatment for open-angle glaucoma, particularly in those treated with timolol eyedrops. An excess cardiovascular mortality (28 percent) was also associated with those participants with ocular hypertension at the beginning of the study.
The authors suggest that excess mortality found in persons with previously diagnosed open-angle glaucoma could be due to their longer duration of disease compared with those with newly diagnosed disease. Adverse effects or inappropriate use of beta blockers and other medications used to treat open-angle glaucoma may affect the cardiovascular system and possibly increase death risk. However, the association with any timolol use could be a marker for longer duration of treatment and/or more advanced glaucoma, rather than being due to the medication itself.
Lu et al. performed genetic and clinical studies to characterize the disease-causing mutations and associated clinical phenotypes in five families with autosomal dominant congenital fibrosis of the extraocular muscles (CFEOM).
Ophthalmic investigations included visual acuity, levator function, documentation of compensatory head position, ocular motility, and slit-lamp and fundus examinations. The kinesin family member 21A gene (KIF21A) was sequenced for mutation detection. Genotyping and linkage analysis was performed for the KIF21A/FEOM1 and FEOM3 loci.
Four families were clinically classified as CFEOM1 with full expression of severe ptosis and ophthalmoplegia. One family had CFEOM3 with typically varying expression of phenotypes between individuals. Recurrent heterozygous KIF21A mutations were identified in two CFEOM1 families (2860C > T) and the CFEOM3 family (2861G > A). In another CFEOM1 family, a novel missense mutation (84C > G, C28W) was revealed.
The authors’ findings add to the knowledge about KIF21A mutation spectra. The novel KIF21A mutation 84C > G affects the kinesin motor domain, suggesting that mutations may also occur outside the commonly involved coil-coiled domain. The 2861G > A mutation found in a CFEOM3 family previously has been reported in CFEOM1, further suggesting that different phenotypes can arise from identical mutations.
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
In a 10-year study, Frenkel et al. found that intravitreal injections of methotrexate may safely and effectively control vitreoretinal involvement of primary central nervous system lymphoma without serious adverse reactions.
Over the course of a decade, the researchers treated 44 eyes of 26 patients. A dose of 400 µg/0.1 ml of methotrexate was injected at the level of the pars plana using a 30-gauge needle under topical anesthesia with both topical benoxinate hydrochloride 0.4 percent drops and amethocaine hydrochloride 0.5 percent drops. Patients received these injections twice weekly for four weeks, once weekly for eight weeks and then once monthly for nine months, for a total of 25 injections.
Overall, clinical remission was reached after 6.4 injections of methotrexate, with 95 percent of the eyes needing 13 injections or less to be cleared of malignant cells. None of the patients experienced an intraocular recurrence. All patients developed conjunctival hyperemia and some form of keratopathy. The most common side effect was corneal epitheliopathy. The researchers conclude that these findings demonstrate the proposed protocol represents a good first-line treatment option for vitreoretinal lymphoma.
While techniques to implant IOLs have advanced considerably, the ability to calculate biometric data of the eye before IOL implantation continues to be a challenge. In addition, correctly positioning the IOL during surgery, unpredictable wound healing results and possible postoperative migration of the IOL make optimal vision difficult to predict and achieve.
To address these issues, Träger et al. report on significant improvements in the material properties of polymers for IOLs whose refractive index can be fine-tuned noninvasively in vivo to make focal-length and aspheric corrections.
Specifically, while copolymerization with butyl methacrylate did not demonstrate the desired effects, the introduction of aliphatic spacers of varying length between the polymer backbone and the coumarin moieties led to significant improvements. The researchers note these polymers are the first to combine a high initial refractive index, a high photoinduced refractive index change, a low glass transition temperature and a high transparency in the visible wavelength regime. This translates into materials that would enable a surgeon to tune the focal length of a standard IOL by 2 diopters—thus helping patients to achieve better vision after cataract surgery.
While researchers have demonstrated the potential of retinal cell transplantation to restore visual function in animal models, obtaining a sufficient supply of these cells has proven challenging.
Osakada et al. found that generating rod and cone photoreceptors from mouse, monkey and human embryonic stem cells may one day address this issue, allowing for the development of human embryonic stem cell–based therapies for retinal diseases.
Putative rod and cone photoreceptors were generated through stepwise treatments under defined culture conditions—in the absence of retinal tissue. With the mouse embryonic stem cells, Crx+ photoreceptor precursors were induced from Rx+ retinal progenitors through treatment with a Notch signal inhibitor. Next, application of fibroblast growth factors, Shh, taurine and retinoic acid resulted in a greater number of rhodopsin+ rod photoreceptors in addition to default cone production. Other stepwise treatments were performed to generate monkey and human embryonic stem cells.
Roundup of Other Journals is written by Lori Baker Schena and edited by Deepak P. Edward, MD.