American Academy of Ophthalmology Web Site: www.aao.org
New Findings from Ophthalmology, AJO and Archives
September’s American Journal of Ophthalmology:
August’s American Journal of Ophthalmology:
July’s Archives of Ophthalmology:
June’s Archives of Ophthalmology:
Roundup of Other Journals:
The Diabetic Retinopathy Clinical Research Network has shown that after two years, focal/grid photocoagulation is more effective and demonstrates fewer side effects than 1-mg or 4-mg doses of preservative-free intravitreal triamcinolone in patients with diabetic macular edema.
This study included 693 participants (840 eyes) with DME involving the fovea and with visual acuity between 20/40 and 20/230. They were randomized to focal/grid photocoagulation, 1 mg of intravitreal triamcinolone or 4 mg of intravitreal triamcinolone. At four months, the mean visual acuity was better in the 4-mg triamcinolone group. Yet by one year, there were no significant differences among groups in mean visual acuity. By two years, focal/grid photocoagulation was not only more effective than triamcinolone in visual acuity and OCT-measured retinal thickening, but was also associated with fewer side effects, including lens changes and elevation of IOP.
The authors conclude that focal/grid photocoagulation should be the benchmark against which other treatments are compared in DME clinical trials.
Graft detachment is the most common type of complication associated with Descemet’s stripping automated endothelial keratoplasty (DSAEK), according to a case series by Suh et al. involving 118 eyes of 99 patients in one university practice.
In this study, 64 eyes had pseudophakic bullous keratopathy, 41 eyes had Fuchs’ endothelial dystrophy and cataract, three eyes had aphakic bullous keratopathy and 10 eyes were from previous DSAEK failures. Graft detachments were observed in 27 of the 118 eyes (23 percent). Thirteen of the 17 reattached grafts had subsequent clearing of the cornea. Other complications included graft failure, graft rejection, cystoid macular edema, retinal detachment, suprachoroidal hemorrhage and pupillary block. The total number of DSAEK failures or persistent edema after the DSAEK procedure was 21 eyes (17 percent).
The authors conclude that DSAEK is a viable alternative to traditional penetrating keratoplasty, yet the learning curve for this procedure may be steep and the potential for complications significant.
Using a U.S. database of participants aged 60 and older, Motsko and Jones found no association between hypothyroidism and open-angle glaucoma (OAG).
The investigators matched 4,728 newly diagnosed OAG patients to 14,184 controls based on age and gender. They identified prior hypothyroidism in 815 (17.2 percent) of the OAG patients and in 2,498 (17.6 percent) of the controls. After adjusting for various risk factors such as ischemic heart disease and hypertension, patients with OAG were not found to be associated with a prior hypothyroid diagnosis when compared with the controls.
The authors conclude that the large proportion of patients receiving thyroid replacement therapy may have negated any OAG-related consequences of hypothyroidism. However, a secondary analysis of untreated hypothyroidism showed a nonsignificant trend toward an increased risk of developing OAG compared with the treated patients.
The Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) Research Group has found that increased age and focal hyperpigmentation represent risk factors for the development of choroidal neovascularization and geographic atrophy in eyes with large drusen.
The 1,052 participants with 10 or more large drusen and visual acuity greater than or equal to 20/40 in each eye were a cohort in a clinical trial of laser treatment for the prevention of vision loss from advanced age-related macular degeneration. The CAPT group found the risk factors for choroidal neovascularization in the multivariate model for all eyes were older age, cigarette smoking and focal hyperpigmentation. Risk factors for geographic atrophy were older age, greater retinal area covered by drusen, retinal pigment epithelium depigmentation and focal hyperpigmentation.
The researchers note that studies are currently under way to further define the role of these risk factors along with genetic influences in the development of advanced AMD.
Kohnen et al. evaluated whether optic edge design constitutes a long-term factor for posterior capsular opacification (PCO). Their findings suggest that modern foldable IOLs have a low incidence of PCO after three years, with less PCO occurring in sharp optic edge designs—independent of IOL material.
In this open-label clinical trial of aged cataract patients, a high-refractive index silicone IOL with a sharp optic edge (CeeOn) was compared with either a high-refractive index silicone IOL with a round optic edge (PhacoFlex S140NB) in 108 patients or an acrylic IOL with a sharp optic edge (AcrySof) in 139 individuals. PCO was evaluated through cumulative incidence of Nd:YAG laser treatment.
The researchers found that the rate of Nd:YAG laser capsulotomy was 2.1 percent for CeeOn compared with 2.1 percent for Acrysof, and 5.7 percent for CeeOn compared with 17 percent for S140. The authors conclude that the new generation materials are equivalently effective in preventing PCO.
Long-held beliefs that age-related macular degeneration is less common in Asians than in Caucasians were not supported in a study by Kawasaki et al. comparing both populations.
Using age-standardization and direct comparability of results, the researchers compared data from the Funagata Study, a population-based study of 1,758 Japanese persons, with the Blue Mountains Eye Study (BMES), a population-based study of an Australian white population. The prevalence of early AMD in the Funagata Study (4.1 percent) was similar to that in the BMES (4.4 percent). For men in the Funagata Study, the prevalence of late AMD (1.1 percent) was also comparable to that in the BMES (1.2 percent). For women, however, prevalence of late AMD in the Funagata Study was lower than that in the BMES (0.3 percent and 2.1 percent, respectively).
The researchers also documented two consistent AMD risk factors in the Japanese population: increasing age and current smoking, which is consistent with studies in Caucasian subjects. They conclude their study does not support the suppositions that AMD is uncommon in Japan or is unrelated to cigarette smoking.
In an effort to avoid performing enucleation in young patients with advanced intraocular retinoblastoma, Abramson et al. developed a novel technique involving selective ophthalmic artery infusion with local high-dose chemotherapy.
Ten children with advanced intraocular retinoblastoma who required enucleation participated in this phase 1/2 clinical trial. While the children were under anesthesia and receiving anti-coagulation medication, the researchers performed cannulation of their ophthalmic artery through a femoral artery approach using microcatheters. The ophthalmic arteries were successfully cannulated in nine patients—as many as six times in one patient. Dramatic regression of tumors, vitreous seeds and subretinal seeds were observed in each case. Despite the high concentrations of drug delivery to the ocular structures, the incidence of local and systemic complications remained low. Among the first nine successfully treated patients, seven eyes destined to be enucleated were salvaged.
The investigators conclude that this technique has potential to allow many globes currently being enucleated to be salvaged in patients with advanced intraocular retinoblastoma.
American Journal of Ophthalmology
Mansour et al. assessed the role of bevacizumab in inflammatory ocular neovascularization in a case series of patients who were diagnosed with neovascularization from varying causes and for whom standard therapy had failed.
At the three-month follow-up, 84 eyes of 79 patients had been treated with a mean of 1.3 injections of intravitreal bevacizumab. Thirty-four eyes showed juxtafoveal choroidal neovascularization (CNV), 34 eyes showed subfoveal CNV, eight eyes showed peripapillary CNV and 11 eyes showed neovascularization of the disc or neovascularization elsewhere. BCVA improved by one to three lines in 34 percent of the eyes, by four to six lines in 17 percent of the eyes and by more than six lines in 14 percent of the eyes. BCVA worsened in 11 percent. Central foveal thickness decreased from 346 µm at baseline to 252 µm. For CNV, 32 eyes (43 percent) had complete regression after the injection, 27 (36.5 percent) had partial regression, five (7 percent) had no response and 10 eyes (13.5 percent) were not evaluated. For neovascularization of the disc or neovascularization elsewhere, seven eyes (64 percent) had complete regression of new vessels, and four eyes (36 percent) had partial regression after the injection.
The authors conclude that intravitreal bevacizumab can lead to significant visual improvement and regression of neovascularization in a wide variety of inflammatory ocular diseases.
Gartaganis et al. investigated the nature and biochemical mechanisms leading to late opacification of implanted hydrophilic acrylic IOLs.
Thirty of these IOLs were explanted one to 12 years postimplantation due to gradual opacification of the lens material. A materials analysis was done using scanning electron microscopy equipped with a microanalysis probe, confocal microscopy, x-ray diffraction and Fourier transform infrared for the identification of the substances involved in the opacified lenses.
Investigation showed platelike prismatic nanoparticle deposits of calcium phosphate crystallites on the surface and in the interior of opacified IOLs. The platelike deposits exhibited morphology and particle size typical for octacalcium phosphate, while the respective characteristics of the prismatic nanocrystals were typical of hydroxyapatite. Analysis confirmed the chemical composition of the deposits. Aqueous humor analysis showed that the humor was supersaturated with respect to both octacalcium phosphate and hydroxyapatite, favoring the formation of the thermodynamically more stable hydroxyapatite, while the formation and kinetic stabilization of other transient phases was also very likely. In vitro experiments using polyacrylic materials confirmed the clinical findings.
Mason et al. evaluated the visual prognosis of eyes with branch retinal artery occlusion (BRAO).
The authors examined 52 consecutive eyes of 52 patients with BRAO (only eyes with decreased central macular perfusion on fluorescein angiography were included).
On presentation, 54 percent of eyes with BRAO had BCVA of 20/40 or better. At follow-up (mean, 14 months), 60 percent of all eyes had visual acuity of 20/40 or better. Visual acuities of 20/40 or better were retained by 89 percent of eyes with baseline BCVA of 20/40 or better. Only 14 percent of eyes with 20/100 or worse BCVA improved to 20/40 or better. Neither visible emboli nor the region of macular involvement was significant with respect to visual improvement.
The authors conclude that visual prognosis after BRAO seems to be correlated to presenting visual acuity. Eyes with initial visual acuity of 20/40 or better usually remained at 20/40 or better. Individuals with poor visual acuity of 20/100 or worse generally did not show the significant improvement reported in previous studies.
Ramchandran et al. studied the effect of an intravitreal fluocinolone acetonide sustained drug delivery implant in eyes with central retinal vein occlusion (CRVO) and chronic refractory macular edema.
In a prospective case series, 14 eyes of 14 patients with chronically persistent macular edema associated with CRVO underwent intraocular implantation of a three-year fluocinolone acetonide sustained drug delivery system. Visual acuity, central foveal thickness and IOP were monitored in the first 12 months after implant insertion.
At baseline, the median visual acuity was 20/126, improved to 20/60 by two months and was 20/80 by 12 months. A significant proportion of eyes had gained lines of visual acuity at 12 months compared with baseline. At 12 months, the mean and median central retinal thickness decreased from 622 and 600 µm before surgery, respectively, to 307 and 199 µm after surgery, respectively. By 12 months, cataract had developed in all five phakic patients, and 13 of 14 eyes required medical or surgical IOP-lowering interventions.
Alvarado et al. evaluated the long-term outcomes after Ahmed valve implantation when using adjunctive intraoperative mitomycin C and postoperative 5-fluorouracil.
Patients in this retrospective consecutive case series received either the Ahmed valve implantation alone (Ahmed eyes) or in combination with cataract surgery (Ahmed-phaco eyes), using both intraoperative MMC and postoperative 5-fluorouracil. A total of 130 eyes underwent Ahmed valve implantation with intraoperative exposure to 0.5 mg/ml MMC and postoperative subconjunctival injections of 5 mg of 5-fluorouracil. Kaplan-Meier estimates of the cumulative probability of valve success at the sixth follow-up year were 0.72 for Ahmed eyes and 0.84 for Ahmed-phaco eyes. A median of two fewer medications was required relative to baseline for both Ahmed and Ahmed-phaco eyes.
The authors conclude that the adjunctive use of both intraoperative MMC and postoperative 5-fluorouracil with Ahmed valve implantation results in high success rates. IOP was well controlled in the majority of patients within the six-year postoperative period.
Gupta et al. reported the initial experience and safety profile of 23-gauge pars plana vitrectomy in eyes undergoing vitreoretinal surgery.
The inclusion criteria for this study included eyes that underwent primary 23-gauge pars plana vitrectomy for various indications including, but not limited to, epiretinal membrane, nonclearing vitreous hemorrhage, idiopathic macular hole and rhegmatogenous retinal detachment. Exclusion criteria included history of prior vitrectomy, conversion to 20-gauge instrumentation, glaucoma filtration surgery or administration of gas at expansile concentrations.
Ninety-two patients met the inclusion criteria. The overall visual acuity improved from 20/238 preoperatively to 20/82 postoperatively. Intraoperative complications included retinal tears in two eyes. Sclerotomy sutures were also required intraoperatively in two eyes. Postoperative complications included hypotony in six eyes, a retinal tear in one eye and a recurrent retinal detachment in one eye. No cases of endophthalmitis were observed.
The authors conclude that intraoperative and postoperative complications were rare in this series of 23-gauge vitrectomy. Hypotony at postoperative day one was the most common complication observed, and all cases resolved at postoperative week one without intervention. Retinal tear or detachment was an uncommon complication in the intraoperative and postoperative settings.
Archives of Ophthalmology
Sihota et al. evaluated 92 eyes with closed globe injury over a six-month period. While 42 eyes had chronically elevated IOP greater than 21 mmHg, 50 eyes had no evidence of raised IOP. Goniophotography and ultrasound biomicroscopy were performed four weeks subsequent to trauma in all eyes.
The grade of trabecular pigmentation was significantly more in eyes with traumatic glaucoma compared with those without glaucoma. Those with greater than grade 3 pigmentation after trauma had 20 times the risk of developing glaucoma compared with those with lesser pigmentation of the angle. A widened angle recess on ultrasound biomicroscopy increased the risk of developing glaucoma by 30 times.
Other risk factors for developing glaucoma included hyphema, higher baseline IOP at presentation, lens displacement and greater angle recession. Presence of cyclodialysis, however, was protective against the development of traumatic glaucoma.
The authors conclude that apart from the presence of hyphema, lens displacement and greater angle recession, trabecular pigmentation and a widened angle recess signify greater severity of trauma and should be looked for in eyes with closed globe injury. The presence of these even in the absence of other signs of trauma indicates a high probability of developing traumatic glaucoma.
Lam et al. examined the relationship between visual impairment and suicide by using data from the 1986– 1996 National Health Interview Survey with National Death Index mortality linkage through 2002.
Data from 137,479 adult participants were analyzed using structural equation modeling. The average follow-up was 11 years and 200 suicide deaths were identified. After controlling for survey design, age, sex, race, marital status, number of nonocular health conditions and self-rated health, the risk of suicide for those who reported visual impairment was 50 percent greater than those with no reported visual impairment. This finding was not statistically significant. However, the effect of reported visual impairment on suicide indirectly through poorer self-rated health or through a number of nonocular health conditions was statistically significant.
The authors conclude visual impairment may be associated with an increased risk of suicide through its effect on poor health. This suggests improved treatments of visual impairment and factors causing poor health may potentially reduce suicide risk.
Johnson et al. examined how aqueous humor dynamics are affected by exfoliation syndrome with or without elevated IOP. Eighty participants were divided into four groups including 25 patients with exfoliation syndrome with normal IOPs, 25 age-matched healthy controls with normal IOPs, 15 patients with exfoliation syndrome with elevated IOPs and 15 age-matched controls without exfoliation syndrome but with elevated IOPs. Assessments included IOP, episcleral venous pressure, aqueous flow, outflow facility and uveoscleral outflow.
The authors of the study found that uveoscleral outflow was significantly decreased in exfoliation syndrome compared with age-matched controls and was independent of IOP. Patients with elevated IOPs, either with or without exfoliation syndrome, exhibited decreased outflow facility when compared with those with normal IOPs, either with or without exfoliation syndrome. Aqueous flow was neither affected by the level of IOP nor by the presence of exfoliation syndrome.
The authors conclude that exfoliation syndrome in normotensive and hypertensive eyes is associated with decreased uveoscleral outflow. On the other hand, ocular hypertension with or without exfoliation syndrome is associated with reduced outflow facility.
Silva et al. examined the long-term efficacy of the Artisan phakic IOL for the correction of high myopia. Fifteen patients (26 eyes) underwent correction of high (–6 to –9 D) or extreme (greater than –9 D) myopia with placement of the IOL. While being evaluated over five years following their surgeries, a full assessment of visual acuity, refraction, tonometry, corneal topography, slit-lamp biomicroscopy and corneal endothelial cell density was conducted.
Patients were examined five times during the first postoperative year and then once every subsequent year for a total of five years with data from 12 patients (19 eyes) available at the conclusion of the study. At that time, the mean manifest refraction was –0.37 ± 0.69 D with 95 percent of eyes within 1 D of attempted correction.
In addition, 95 percent of eyes achieved an uncorrected visual acuity of 20/40 or better and no eyes experienced a loss of one or more Snellen lines of BCVA. Compared with preoperative measurements, the mean loss of endothelial cells noted over five years was 14.05 percent.
The authors conclude that the Artisan phakic IOL has had excellent predictability, stability and efficacy at reducing high and extreme myopia over five years, but may result in rates of endothelial cells loss that are somewhat higher than have been previously reported in the literature.
Kivlin et al. examined the eyes of 10 patients who died in automobile crashes.
Eight patients had retinal hemorrhages extending into the periphery. Three had elevated circular retinal folds. Six had subinternal limiting membrane hemorrhages, but none had deeper splitting of the retina. Nine had optic nerve sheath hemorrhages. The possible mechanisms causing the hemorrhages include mechanical vitreous traction on the retina and a sudden increase in venous pressure in the retinal vessels.
The authors conclude that the association of extensive, sometimes severe, ocular hemorrhages with fatal accidental trauma (compared with previous reports of accidental trauma with no or few hemorrhages) indicates the severity of injury required to cause hemorrhages of this magnitude.
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
Findings from a study by Ang et al. indicate the alterations to the biomechanical properties of the cornea may occur as a result of chronic raised IOP in primary open-angle glaucoma (POAG).
The researchers evaluated 40 patients with normal-tension glaucoma (NTG) and 41 patients with POAG for corneal hysteresis and corneal resistance factor. They excluded patients with previous intraocular surgery, corneal pathology, inflammatory connective tissue disease and refraction of 5 D or over. Results showed a statistically significant difference in the mean corneal hysteresis between POAG and NTG with the corneal hysteresis higher in patients with NTG. In addition, the highest Goldmann applanation IOP was statistically associated with lower corneal hysteresis and higher corneal resistance factor.
The researchers conclude that these small but statistically significant differences may be a result of chronically raised IOP in POAG. Further research is necessary to determine how these biomechanical corneal changes affect the development and progression of glaucoma.
While the literature has shown that intravitreal triamcinolone acetonide improves diabetic macular edema, Hauser et al. found the optimal dose has yet to be determined.
The researchers conducted a randomized study comparing three different doses of intravitreal triamcinolone—1 mg, 2 mg and 4 mg—in 45 eyes with refractory diffuse diabetic macular edema with cystic changes. Forty-two eyes completed the six-month follow-up.
At four weeks, all three groups improved between eight and nine Early Treatment Diabetic Retinopathy Study letters with a partial remission at 12 weeks. While the 1-mg and 2-mg groups showed no further remission at 24 weeks, the 4-mg group showed slight remission. The standardized central macular thickness improved in all three groups at four weeks, an improvement that continued through 12 and 24 weeks in the 1-mg and 2-mg groups but not in the 4-mg group.
The authors conclude the 4-mg dose of intravitreal triamcinolone does not have enough advantages over the other two doses to warrant its use. They personally use vehicle-free preparation in doses of 2 mg and maintain that further study is needed to discover the optimal dose.
Two articles published in the New England Journal of Medicine, on the use of gene transfer technology to treat Leber’s Congenital Amaurosis (LCA) caught the attention of David A. Williams, MD, editor-in-chief of Molecular Therapy, who wrote an editorial in his journal on the studies’ findings. Dr. Williams notes that the cautiously optimistic results by the two groups of researchers highlight advances being made in this area of research and that the treatment approach deserves further exploration.
In one study, Bainbridge et al. gave three patients with LCA subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA under the control of a human RPE65 promoter. None of these patients experienced significant change in visual acuity or in peripheral visual fields, and no change was detected in retinal responses on electroretinography. However, one patient did experience improvement in visual function on microperimetry and on dark-adapted perimetry, and improvement in a subjective test of visual mobility.
Maguire et al. also studied three patients with LCA using the AAV vector expressing RPE65 complementary DNA. This vector involved the chicken beta-actin promoter. Each of the three eyes that received the injection became more effective in driving the pupillary response and became about three times as sensitive to light from baseline. There were also gains in visual acuity at six weeks with slower rates of improvement afterward.
Roundup of Other Journals is written by Lori Baker Schena and edited by Deepak P. Edward, MD.