December's American Journal of Ophthalmology:
November's Archives of Ophthalmology:
Roundup of Other Journals:
Toric Implantable Collamer Lens Shown Effective and Safe in FDA Trial
Results from the clinical trial of the Toric implantable collamer lens (ICL) to treat moderate to high myopic astigmatism indicate that the lens is effective and safe.
The trial involved 210 eyes of 124 patients. The eyes were between 2.38 and 19.5 D of myopia and 1 to 4 D of astigmatism and implanted with the Toric ICL. Sanders et al. report postoperative uncorrected visual acuity was 20/20 or better in 83.1 percent of eyes, while the mean manifest refractive cylinder dropped from 1.93 D at baseline to 0.51 D postoperatively. This represented a 73.6 percent decrease in astigmatism. Postoperatively, 37.6 percent of eyes had a BCVA of 20/12.5 or better, compared with 4.8 percent preoperatively.
The authors conclude that these findings support the efficacy and predictability of Toric ICL implantation to treat moderate to high myopic astigmatism.
Primary Scleral-Fixated vs. Anterior Chamber IOL Implantation
In the event of inadequate posterior capsular support during a cataract operation, the intraocular lens can be placed in the sulcus if the capsule-zonular rim is intact.
If adequate sulcus support is absent, the surgeon may choose to implant a primary scleral-fixated intraocular lens (SFIOL) or a primary anterior chamber intraocular lens (ACIOL).
Kwong et al. conducted a retrospective, comparative case series in 36 eyes of 36 patients with SFIOLs and 46 eyes of 46 patients with ACIOLs to determine which lens resulted in a better postoperative BCVA. They found that 71.7 percent of eyes in the ACIOL groups achieved a postoperative Snellen BCVA of 20/40 or better compared with 47.2 percent of eyes in the SFIOL group.
The authors call for prospective trials with longer follow-up to better evaluate implantation of these two lenses.
IOP-Lowering Effect of Adding Dorzolamide or Latanoprost to Timolol
The potential to achieve a lower IOP with combined medical therapy in patients with primary open-angle glaucoma (POAG) prompted Webers et al. to conduct a meta-analysis to estimate the IOP-lowering effect of 2 percent dorzolamide or 0.005 percent latanoprost when added to 0.5 percent timolol.
After reviewing 17 articles, the investigators found that the addition of these two therapeutic agents further lowers IOP in eyes treated with timolol. In an attempt to extrapolate these results to clinical practice, the investigators chose only studies that included patients with POAG or ocular hypertension in at least 85 percent of cases. They also included studies on both the concomitant and fixed combined use.
Nevertheless, the authors caution that the results may not be generalizable because these trials may have included nonresponders to timolol.
Topical Cyclosporine Treatment May Be Cure for Dry Eye Disease
Wilson and Perry report that topical cyclosporine A appears to be associated with a cure of symptoms and signs in a subgroup of chronic dry eye patients. In this study, eight patients who had suffered with chronic dry eye disease from three to 30 years were treated with topical 0.05 percent cyclosporine A with or without topical corticosteroids twice a day as well as with nonpreserved artificial tears for six to 72 months. These eight patients were free of signs or symptoms of dry eye disease for a minimum of one year after completing their course of therapy.
The authors note that while most dry eye patients do seem to have a return of symptoms and signs a few weeks to months after discontinuing anti-inflammatory treatment, this subgroup of patients had no return of symptoms—indicating a possible cure with cyclosporine A treatment.
The next step is to determine through a large, prospective, multicenter trial whether this treatment approach can prevent progression of dry eye disease in patients with early, mild symptoms.
10-Year Incidence of Age-Related Maculopathy in Blue Mountains Eye Study
Long-term results from the Blue Mountains Eye Study indicate that the risk of age-related maculopathy (ARM) progression is strongly related to the severity of early-stage lesions.
Wang et al. originally examined 3,643 participants aged 49 and older in 1992. They reexamined 2,335 survivors after five years and 1,952 survivors after 10 years. The same graders performed retinal photographic grading in all exams, using the Wisconsin ARM Grading System. Sixty-seven patients at risk of late ARM were reexamined at either or both follow-up time points. Over the 10-year period, 3.7 percent developed late ARM and 14.1 percent developed early ARM. After age-standardization to the Beaver Dam Eye Study population, the 10-year incidence of late and early ARM was 2.8 percent and 10.8 percent, respectively. Baseline age and early ARM lesion characteristics and severity were strong predictors of later ARM incidence.
The authors conclude that this study provides evidence-based criteria for identifying persons at high risk of developing late ARM.
American Journal of Ophthalmology
Tube vs. Trabeculectomy Study: One-Year Follow-Up
Poor glaucoma control following cataract or glaucoma surgery is an especially difficult scenario. The Tube vs. Trabeculectomy Study Group was formed to elucidate preferred surgical options.
Gedde et al. report the one-year results of a multicenter, randomized clinical trial in 17 clinical centers. Patients had uncontrolled glaucoma on maximum tolerated medical therapy and had previously undergone either trabeculectomy or cataract extraction with IOL implantation. They were randomized to either a 350-mm2 Baerveldt glaucoma implant or trabeculectomy with mitomycin C (MMC).
A total of 212 eyes of 212 patients were enrolled, including 107 in the tube group and 105 in the trabeculectomy group. At one year, mean IOP was 12.4 mmHg in the tube group and 12.7 mmHg in the trabeculectomy group (P = 0.73). The mean number of glaucoma medications being taken was 1.3 in the tube group and 0.5 in the trabeculectomy group (P < 0.001). The cumulative probability of failure during the first year of follow-up was 3.9 percent in the tube group and 13.5 percent in the trabeculectomy group (P = 0.017).
Nonvalved tube shunt surgery was more likely to maintain IOP control and avoid persistent hypotony or reoperation for glaucoma than trabeculectomy with MMC during the first year of follow-up.
Both surgical procedures produced similar IOP reduction at one year, but there was less need for supplemental medical therapy following trabeculectomy with MMC.
Tube vs. Trabeculectomy Study: Complications During Follow-Up
In a separate report from the database above, Gedde et al. report the intraoperative and postoperative complications encountered during the first year of follow-up.
Intraoperative complications occurred in seven of the 107 patients (7 percent) in the 350-mm2 Baerveldt tube group and 10 of the 105 patients (10 percent) in the trabeculectomy with mitomycin C group (P = 0.59). Postoperative complications developed in 36 patients (34 percent) in the tube group and 60 patients (57 percent) in the trabeculectomy group during the first year of follow-up (P = 0.001). Surgical complications were associated with reoperation and/or loss of greater than 2 lines of Snellen visual acuity in 18 patients (17 percent) in the tube group and 28 patients (27 percent) in the trabeculectomy group (P = 0.12).
There appears to be a large number of surgical complications during the first year of follow-up in the study, but most seem self-limited. The incidence of postoperative complications was higher after trabeculectomy with MMC than nonvalved tube shunt surgery. Serious complications resulting in reoperation and/or vision loss occurred with similar frequency with both surgical procedures.
Phacoemulsification vs. Manual Sutureless Small Incision in Nepal
Ruit et al. compared the efficacy and visual results of phacoemulsification with those of manual sutureless small incision extracapsular cataract surgery (SICS) for the treatment of cataracts in Nepal.
This was a prospective, randomized comparison of 108 consecutive patients with visually significant cataracts. Patients were assigned randomly to receive either phacoemulsification or SICS, both with placement of an IOL.
Both surgical techniques achieved excellent outcomes with low complication rates. The SICS group had less corneal edema on postoperative day one. At six months, 89 percent of the patients with SICS had uncorrected visual acuity of greater than 20/60, and 98 percent of the patients had a best-corrected vision of greater than 20/60. In the other group, 85 percent had a UCVA of greater than 20/60 and 98 percent a BCVA of greater than 20/60 (P = 0.30). Surgical time for SICS was much shorter than for phacoemulsification (P < 0.0001).
Both phacoemulsification and SICS achieved excellent visual outcomes with low complication rates. SICS is significantly faster, less expensive and less technology-dependent than phacoemulsification.
Corneal Biomechanics and IOP Before and After LASIK
The cornea experiences significant biomechanical changes from LASIK that are reflected in IOP measurements. Pepose et al. compared the preoperative and postoperative measurement of corneal biomechanical properties and IOP by using the Goldmann applanation tonometry (GAT), the ocular response analyzer (ORA) and the Pascal dynamic contour tonometer (PDCT) in eyes undergoing myopic LASIK.
The IOP was measured in 66 myopic eyes before and after LASIK by GAT, ORA and PDCT in a randomized sequence in a prospective, nonrandomized clinical trial. The researchers recorded metrics for the following corneal biomechanical properties: corneal hysteresis (CH), corneal resistance factor (CRF) and ocular pulse amplitude (OPA).
After LASIK, there was a reduction in mean corneal pachymetry of 90.2 µm and in IOP measurements with GAT (Δ = –1.8 ± 2.8 mmHg; P < 0.01), ORA-Goldmann (Δ = –4.6 ± 2.8 mmHg; P < 0.01) and ORA–corneal compensated (Δ = –2.1 ± 2.6 mmHg; P < 0.05). There was no statistically significant difference between preoperative and postoperative IOP measurements taken by PDCT. Postoperatively, CRF decreased by 28.6 percent (P < 0.01), CH by 16.2 percent (P < 0.01) and OPA by 1.8 percent (P = 0.32).
Measurement of IOP with PDCT appears to be relatively immune to changes in corneal biomechanics and pachymetry after LASIK, in comparison to GAT and ORA measures of IOP. PDCT and ORA both showed statistically lower variation in measurement than GAT. LASIK produced a marked decline in CH and CRF, which may reflect respective changes in the viscous and elastic qualities of the post-LASIK cornea. In contrast, there was no statistical change in OPA.
Autologous Serum-Derived Cultivated Oral Epithelium Transplantation for Severe Ocular Surface Disease
Ang et al. evaluated the use of autologous serum (AS)-derived cultivated oral epithelium transplantation for the treatment of severe ocular surface disease.
AS from 10 patients with severe ocular surface disease and total limbal stem cell deficiency was used in developing autologous cultivated oral epithelial equivalents. These were compared with others derived from conventional fetal bovine serum (FBS)-supplemented medium. Surgery involved removal of the corneal pannus and surrounding diseased tissue, and implantation of the AS-derived epithelial equivalents. The oral equivalents were then analyzed by histology and immunohistochemistry.
Oral epithelial sheets cultivated in AS- and FBS-supplemented media were similar in morphology and formed basement-membrane assembly proteins important for maintaining graft integrity. Complete corneal epithelialization was achieved within two to five days postoperatively. The ocular surface remained stable without major complications in all eyes during a mean follow-up period of 12.6 ± 3.9 months. The visual acuity improved by more than two lines in nine out of 10 eyes, with transplanted oral epithelium surviving up to 19 months.
The authors demonstrated the successful use of an AS-derived oral epithelial equivalent to treat severe ocular surface disease and have brought us one step closer toward developing safer, bioengineered products that are completely derived from the patient’s own tissue.
Central Corneal Thickness and Changes in the Optic Nerve Head Following IOP Reduction in Glaucoma and Ocular Hypertension
Lesk et. al. examined the relationship between central corneal thickness and optic nerve head biomechanics in 32 subjects with open-angle glaucoma and ocular hypertension. Optic nerve head biomechanics were evaluated by measuring changes in the depth of the cup following IOP-reduction using confocal scanning laser ophthalmoscopy. Changes in neuroretinal rim blood flow were also evaluated using scanning laser Doppler flowmetry.
Eyes with thinner corneas had a significantly greater mean reduction in cup depth upon IOP reduction compared with those with thicker corneas. Eyes with thinner corneas also had significantly smaller increases in neuroretinal rim blood flow.
The authors conclude that the primary structure determining cup depth, the lamina cribrosa, may be more mobile in patients with thinner corneas and that this mobility, along with the thinner corneas’ associated vascular phenomenon, may contribute to the development of glaucoma.
Ranibizumab With Verteporfin in Neovascular AMD
Heier et al. compared the safety and efficacy of ranibizumab treatment in conjunction with verteporfin photodynamic therapy (PDT) vs. verteporfin PDT alone in patients with subfoveal, predominantly classic, choroidal neovascularization (CNV) secondary to age-related macular degeneration. Their two-year, phase 1/2, multicenter, randomized, single-masked, controlled trial is designated the FOCUS study. This article describes the results for the first year, which was the point for the primary efficacy analysis. The key efficacy outcome measures were the proportion gaining at least 15 letters letters from baseline visual acuity, the proportion gaining greater than or equal to 15 letters from baseline VA and the mean change in VA.
At 12 months, 90.5 percent of ranibizumab-plus-PDT patients had lost fewer than 15 letters from baseline VA, compared with 67.9 percent of patients treated with PDT alone (P = 0.0003). In addition, 23.8 percent of ranibizumab-plus-PDT patients had gained at least 15 letters from baseline VA, compared with only 5.4 percent who received PDT alone (P = 0.003). For the mean change from baseline VA, the clinical benefit from ranibizumab-plus-PDT over PDT alone was seen by the third month of treatment (P = 0.01) and was statistically significant at each subsequent monthly assessment. By 12 months, the difference between the two groups was 13.1 letters, from a mean gain of 4.9 letters in the ranibizumab-plus-PDT group to a mean loss of 8.2 letters in the PDT-alone group (P < 0.001).
The most frequent ranibizumab-associated serious ocular adverse events were intraocular inflammation (11.4 percent) and endophthalmitis (1.9 percent; 4.8 percent if including cases that were retrospectively presumed to be endophthalmitis but were not reported by the investigator as such). Nevertheless, on average, ranibizumab-plus-PDT patients with serious inflammation still had better VA outcomes than PDT-alone patients at 12 months. Key serious nonocular adverse events included myocardial infarctions (3.6 percent in the PDT-alone group vs. 0 in the ranibizumab-plus-PDT group) and cerebrovascular incidents (3.8 percent in the ranibizumab-plus-PDT group vs. 0 in the PDT-alone group).
The authors conclude that ranibizumab in conjunction with PDT was more effective than PDT alone in treating neovascular AMD characterized by predominantly classic CNV. Because the study design did not include a treatment arm that received ranibizumab alone, it could not be clearly determined whether this superior efficacy was due to the combination or to ranibizumab alone.
Astigmatism and Anisometropia in Preterm Children During the First 10 Years of Life
Larsson and Holmström examined the development of astigmatism and anisometropia during the first 10 years of life in preterm children who were previously included in a population-based study on the incidence of retinopathy of prematurity.
Cycloplegic retinoscopies were performed in 198 preterm children at six months, 2.5 years and 10 years of age. The development of astigmatism greater than or equal to 1 D and anisometropia greater than or equal to 1 D were analyzed.
The amount and prevalence of astigmatism declined between six months and 2.5 years and then remained stable. No difference in the course of development was found according to the stage of ROP. The amount of anisometropia increased, but its prevalence remained unchanged. Multiple regression analyses showed that astigmatism greater than or equal to 1 D at 2.5 years and cryotreated ROP were risk factors for astigmatism at 10 years, and that anisometropia greater than or equal to 2 D at 2.5 years was a risk factor for anisometropia at 10 years.
The authors conclude that development of astigmatism and anisometropia showed a similar course, regardless of the stage of ROP. The retinoscopy at six months was of no value in predicting astigmatism and anisometropia at 10 years, but the refraction at 2.5 years was. Retinoscopy at about 2.5 years in pre-term children may be useful for detecting astigmatism and anisometropia that will persist in children of school age.
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
Infectious Trachoma Reinfection After Targeted Treatment
The Journal of the American Medical Association
In 1996, the World Health Organization introduced a global strategy to eliminate blinding trachoma by the year 2020. This initiative was called the SAFE strategy—Surgery for trichiasis; Antibiotics for Chlamydia trachomatis infection; Facial cleanliness; and Environmental improvement. Atik et al. conducted a prospective study to evaluate the impact of two annual targeted oral azithromycin treatments on school-aged children and their household members on active trachoma and C. trachomatis infection rates during a three-year period in three randomly selected communes in Vietnam.
Results indicated that reinfection rates increased significantly between 12 and 36 months for SAFE communes, but not for the S-only commune after 24 months. In addition, reinfection risk was significantly higher for SAFE and SA communes at 36 months.
These findings suggest this treatment strategy with oral azithromycin may interrupt the duration of infection required to confer immunity, which in turn increases the number of individuals susceptible to reinfection and adversely affects disease prevalence over time. They call for additional research to assess the spectrum of immune responses at the time of treatment.
Anecortave Acetate Treatment Not Effective for Retinal Angiomatous Proliferation
Klais et al. conducted a study to determine whether anecortave acetate would be effective in the treatment of retinal angiomatous proliferation (RAP), a neovascular form of AMD.
Thirty-four patients with RAP were randomized 1:1:1 for treatment with 30 mg, 15 mg or 3 mg of anecortave acetate suspension by juxtascleral administration. While detachment of the neurosensory retina and retinal pigment epithelium improved in all eyes, all neovascular lesions increased in size, with vision loss occurring in the majority of eyes regardless of the quantity administered. In addition, anecortave acetate affected the permeability but not the vasogenic aspect of the neovascular complex.
They conclude that anecortave acetate alone does not appear to benefit patients with this variant of neovascular AMD.
Phacoemulsification Effective in Patients With Baerveldt Tube Shunts
Journal of Cataract and Refractive Surgery
A retrospective analysis by Erie et al. of nine eyes of eight patients with functioning Baerveldt tube shunts indicates that phacoemulsification to treat cataracts in these individuals improves vision and maintains control of IOP. The patients in this study underwent clear corneal phacoemulsification and were followed for a mean of 21 months.
At one month, the mean change in IOP and the number of glaucoma medications taken did not change significantly. Even at the final follow-up, there were no significant changes. At the last examination, two eyes had IOP increases of 2 to 4 mmHg, three eyes had no change and four eyes had decreases of 4 to 7 mmHg. Visual acuity improved in eight eyes, with a mean improvement of 4 ± 3 Snellen lines. No eye developed corneal decompensation. In addition, similar to other studies, IOP increased in one eye from the entire group after phacoemulsification and required subsequent tube revision.
The authors conclude that phacoemulsification is effective in treating cataracts in individuals with functioning Baerveldt filters, but they caution that the possibility of decreased IOP control and need for additional glaucoma surgery after phacoemulsification should be a concern.
Complement Factor H Haplotype Deletion May Lower Risk of AMD
Hughes et al. have shown that a common complement factor H (CFH) haplotype, with deletion of CFHR1 and CFHR3, actually has a protective effect in age-related macular degeneration. This finding comes on the heels of AMD research breakthroughs in 2005 in which CFH was identified as a major susceptibility gene.
In this research, the investigators genotyped polymorphisms spanning the cluster of CFH and five CFH-related genes on chromosome 1q23 in 173 patients with severe neovascular AMD and 170 elderly controls with no signs of AMD.
Their detailed analysis indicated that a common haplotype that carried a deletion of CFHR1 and CFHR3 was present on 20 percent of chromosomes of the controls and 8 percent of chromosomes of those with AMD. The investigators noted that this protective effect of the deletion haplotype cannot be attributed to linkage disequilibrium with the Y402H polymorphism (that has been proposed as the likely causative factor of AMD) and was replicated in an independent sample.
They conclude that resolving the genetic basis for the different halotypic effects may help shed light on the etiology of AMD and could even result in therapeutic targets for gene silencing.
Roundup of Other Journals is written by Lori Baker Schena and edited by Deepak P. Edward, MD.