American Academy of Ophthalmology Web Site: www.aao.org
New Findings from Ophthalmology, AJO and Archives
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:
Konstas et al. demonstrated that, following six months of therapy, dorzolamide/timolol fixed combination (DTFC) and latanoprost possess similar 24-hour IOP-lowering efficacy.
The researchers randomized 39 patients with primary open-angle glaucoma and 14 patients with ocular hypertension either to six months of treatment with DTFC twice daily or latanoprost every evening. The patients were then crossed over to the opposite treatment for an additional six months. The 53 patients had an average 24-hour baseline IOP of 25.2 ± 2.3 mmHg. The 24-hour IOP was 18.1 ± 1.9 mmHg for the DTFC group and 18.3 ± 1.9 mmHg for the latanoprost group. The DTFC group experienced more burning and a more bitter taste, while the latanoprost group had more hypertrichosis and ocular itching.
While the study shows that both treatments yield similar 24-hour IOP-lowering efficacy, it did not evaluate the long-term results of these medications.
Stewart et al. constructed a Markov model to determine the cost-effectiveness of treating ocular hypertension.
Derived from the Ocular Hypertension Treatment Study (OHTS), the incremental cost-effectiveness ratio (ICER) to prevent one patient with ocular hypertension from progressing to primary open-angle glaucoma was $89,072.
However, adjusting for risk factors identified by multivariate analysis in the OHTS painted a different picture: the minimally cost-effective ICER level was $45,155 for patients 20 years above the average of 56 years; $46,748 for patients 4 mmHg above the average pressure of 25 mmHg; $36,683 for patients with 40 µm less than the average central corneal thickness of 573 µm; and $35,633 for patients with a vertical cup/disc ratio 0.2 wider than the average of 0.4.
Kitzmann et al. conducted a study providing the only known population-based data on the incidence of central serous chorioretinopathy (CSC).
The researchers found that the overall incidence of CSC was 5.8 per 100,000 people. The age-adjusted incidence in males was significantly higher at 9.9 per 100,000 people—about five to six times higher than the incidence in females. The researchers did not find a statistically significant association between CSC and corticosteroid use. Of the patients treated for CSC, 14 percent developed choroidal neovascularization, and all had prior laser photocoagulation.
The investigators did not identify any risk factors associated with the development of CSC, a finding that may be related to the small study size of 74 patients. They call for further research to determine the risk factors for CSC and better understand why men are affected more than women.
As 25-gauge pars plana vitrectomy becomes an increasingly popular technique, Kunimoto et al. set out to assess the incidence rate of endophthalmitis after this surgery and compare it to the endophthalmitis rate of the more traditional 20-gauge procedure.
The investigators conducted a study involving 8,601 consecutive pars plana vitrectomy surgery patients. In this series, 25-gauge vitrectomy had a 12.5-fold higher rate of endophthalmitis than 20-gauge vitrectomy, with one in 434 eyes developing the condition after 25-gauge vitrectomy compared with one in 5,500 eyes with the 20-gauge procedure.
The authors hypothesize that this disparity may be related to wound formation and the lack of wound closure in 25-gauge vitrectomy, as well as possible early postoperative hypotony and minimal vitrectomy with higher amounts of retained vitreous at the end of the procedure. They recommend this study be repeated to validate their findings and perhaps determine the causes of increased risk.
In a trial involving 111 eyes of 111 patients with diabetic macular edema (DME), Lam et al. evaluated the efficacy of intravitreal triamcinolone acetonide (IVTA) followed by grid laser photocoagulation and compared the results to either IVTA or laser alone.
Thirty-seven patients with DME involving the fovea were randomized to grid laser photocoagulation; 38 patients were treated with 4-mg IVTA; and 36 patients received 4-mg IVTA followed by sequential grid laser about one month later. At six-month follow-up, the researchers noted significant reductions in central foveal thickness in both the IVTA and combined groups, but not in the laser group. While BCVA improved significantly at weeks four and nine for the IVTA group, it did not change significantly in the other two groups.
Friedman et al. conducted a population-based observational study involving 1,250 participants of the Salisbury Eye Evaluation Project cohort and compared several tests of mobility performance among individuals with glaucoma to those without the condition.
Individuals performed a series of tasks including navigating a circuitous obstacle course, climbing stairs, performing tandem stands and walking a four-meter course. After adjusting for age, race and gender, results showed that individuals with bilateral glaucoma walked through the obstacle course 2.4 meters per minute slower than those without glaucoma. In addition, these participants experienced 1.65 times the number of bumps compared with the nonglaucoma group. The investigators did not find decreased mobility among those with unilateral glaucoma, a finding that may suggest mobility is not significantly affected until glaucoma becomes bilateral.
Chang et al. utilized a third-generation optical coherence tomography device to assess changes in the peripapillary retinal nerve fiber layer (RNFL) thickness of 21 eyes of 21 glaucoma patients who underwent a medical or surgical intervention to lower IOP.
OCT scans were performed for up to 38 days before intervention and 32 to 74 days after intervention to measure peripapillary RNFL thickness. While 20 of the 21 eyes had an IOP reduction greater than 30 percent, no significant change was seen in the overall RNFL thickness. The authors provide several possible explanations for their findings, especially in light of previous studies using other measurement devices that did find a significant increase in the overall mean RNFL thickness after IOP lowering.
They call for a larger study that includes additional imaging modalities such as scanning laser polarimetry to explain the differences between the studies and to determine whether clinicians need a new baseline measurement of RNFL after IOP has been lowered.
A study by Frick et al. using a managed care claims database highlights the high costs of blindness in the United States. The researchers identified 10,796 patients with blindness and matched them with a cohort of patients without blindness. They calculated total and pharmacy-related direct medical charges in the first year of follow-up for both groups.
For the blind population, the total mean and median health care charges in the first year were $20,677 and $6,854 per person, respectively. In contrast, the nonblind patients had total mean and median health care charges in the first year of $13,321 and $3,778, respectively. The analysis by age group revealed significantly higher overall charges in the older age group—a contrast with the cost of lost productivity studies traditionally used to evaluate the cost of blindness.
American Journal of Ophthalmology
In this study, Alio et al. evaluated the results of corneal wavefront-guided enhancements in patients with night vision symptoms and significantly high positive spherical aberration after myopic laser refractive surgery.
Twenty-eight eyes of 20 patients with significant night vision symptoms and positive corneal spherical aberration (Z40) higher than 0.5 µm after myopic laser refractive surgery were included in the study. Enhancement surgery was planned to remove residual refractive error and corneal spherical aberration (Z40) in all cases. All patients underwent corneal wavefront-guided excimer laser re-treatments using the Schwind Esiris system. The main outcome measures were visual symptoms, change in corneal spherical aberration (Z40) and corneal asphericity (Q-value).
Subjective reports of night vision symptoms were improved in all patients. Mean corneal spherical aberration (Z40) decreased from 0.75 ± 0.19 µm before surgery to 0.43 ± 0.42 µm after surgery (P < 0.001). Mean asphericity in the 4.5-mm zone significantly decreased from 1.02 ± 1.07 before surgery to 0.52 ± 0.88 after surgery (P = 0.008), and the mean asphericity in the 8-mm zone did not change significantly (P = 0.362). The mean spherical equivalent significantly shifted to hyperopia from –0.22 ± 1.14 D before surgery to 0.33 ± 0.54 D after surgery (P = 0.025).
Alio et al. report 10-year outcomes of LASIK for high myopia (greater than 10 D) in a follow-up retrospective, interventional, case-series study.
The study included 196 myopic eyes of 118 patients with a mean preoperative spherical equivalent of –13.95 ± 2.79 D treated with myopic LASIK using the Visx 20/20 excimer laser and the Automated Corneal Shaper microkeratome. All patients were evaluated three months, one year, two years, five years and 10 years postoperatively. The main outcome measures were refractive predictability and stability, mean corneal keratometry, topographical cylinder, safety, efficacy, stability of visual acuity and postoperative complications.
At 10 years, 82 (42 percent) of 196 eyes were within ±1 D and 119 (61 percent) were within ±2 D of emmetropia. Fifty-four (27.5 percent) eyes underwent re-treatments attributable to under correction and/or regression. The myopic regression decreased with time in eyes that did not undergo re-treatment with a mean rate of –0.25 ± 0.18 D per year. Eleven eyes (5 percent) lost more than two lines of BCVA and 40 percent of eyes showed a postoperative uncorrected visual acuity of 20/40 or better. Two eyes (1 percent) with more than 15-D myopic correction developed corneal ectasia.
Rylander and Vold calculated the yearly costs of topical glaucoma medications in order to assist patients and health care providers. This prospective, experimental, laboratory study used the average wholesale price and common dosing patterns to calculate the theoretical yearly cost of glaucoma medications.
The calculated yearly cost ranged from $150.81 for generic timolol maleate 0.5 percent to $697.42 for Cosopt, and as high as $873.98 for a three-times-daily dose of Alphagan P 0.15 percent. Among brand-name beta-blockers, yearly cost ranged between $203.47 for Timoptic 0.5 percent and $657.24 for Betoptic S.
Generic beta-blockers consistently were more economical than their brand-name counterparts. Yearly cost of prostaglandin analogs ranged from $427.69 for Travatan to $577.62 for Lumigan. The two carbonic anhydrase inhibitors Azopt and Trusopt yielded similar economic profiles. Alphagan P 0.15 percent had yearly calculated costs of $559.08 for twice-daily dosing per eye. The generic selective alpha2-agonist brimonidine tartrate 0.2 percent costs approximately $352.89 and $529.34 per year for the respective two- and three-drops daily per eye regimens.
Although costs may differ in various regions of the United States, the nonselective beta-blockers remain the most inexpensive class of glaucoma medications. Bottle size may impact yearly glaucoma medication expenditures. Costs of glaucoma medications may impact decision making in the medical management of glaucoma.
Donaldson et al. investigated the incidence, clinical features, complications and visual prognosis of patients with pars planitis. This retrospective, multicenter, 20-year cohort study was able to analyze almost all patients within Olmsted County, Minn., with a given medical condition. Databases were searched to identify all patients with pars planitis from 1985 through 2004.
Forty-six eyes of 25 patients were evaluated with a mean follow-up of 14.3 years. The incidence of pars planitis was 2.08 per 100,000 persons. The most common complications were epiretinal membrane in 17 eyes (36 percent), cataract in 14 eyes (30.4 percent) and cystoid macular edema in 12 eyes (26.1 percent). Mean visual acuity after 10 years of follow-up was 20/30, with 18 of 24 patients maintaining a visual acuity of 20/40 or better. One-third of patients maintained normal visual acuity without requiring treatment.
The authors conclude that the visual prognosis of pars planitis is relatively good, with 75 percent of patients maintaining a visual acuity of 20/40 or better after 10 years. Many patients in this study with mild disease did not require treatment.
The treatment for central retinal vein occlusion (CRVO) remains elusive with therapies being pursued from many different avenues.
Ferrara et al. evaluated the change in visual acuity and retinal appearance in patients after early initiation of intravitreal bevacizumab treatment for CRVO.
In this case series of six eyes of five patients with recent CRVO (less than three months’ duration), the patients received intravitreal bevacizumab (1.25 mg in 0.05 ml) as primary treatment. Changes in visual acuity, central macular thickness, venous tortuosity and diameter and optic disc edema were recorded.
The mean baseline visual acuity was 20/428 (logMAR units). The mean follow-up period was 12 months, and the number of bevacizumab injections ranged from four to 10. The patients showed a statistically significant decrease in optic nerve head swelling, venous tortuosity and venous diameter, with the largest proportion of change occurring within one month of the first bevacizumab injection.The mean visual acuity at last follow-up was 20/53 (logMAR units). No patient in the study developed collateral vessels at the optic nerve head.
These five patients experienced a dramatic improvement in visual acuity and clinical fundus appearance without collateral vessel formation.
The authors concede that the findings are difficult to explain with current theories of the pathophysiologic features of CRVO but that the results of the study suggest early initiation of anti-VEGF treatment might be studied in a larger trial for CRVO.
In this report, the ANCHOR study group reported the subgroup data from a phase 3 study comparing ranibizumab with verteporfin photodynamic therapy in patients with predominantly classic choroidal neovascularization secondary to age-related macular degeneration. At one year, the data were retrospectively analyzed to identify patient and disease characteristics that may predict visual acuity treatment outcomes.
Univariate analyses were performed to assess visual acuity outcomes across subgroups based on patients’ gender and baseline age, visual acuity score, CNV lesion size, CNV lesion type and duration of neovascular age-related macular degeneration. Multivariate analyses were then performed to identify predictors of the visual acuity change from baseline to 12 months. The proportion of patients losing less than 15 letters, the proportion gaining at least 15 letters, and the mean change from baseline visual acuity were measured and compared.
On average, all subgroups of ranibizumab-treated patients did better than PDT patients for all three visual acuity outcome measures. In the multivariate analyses, lower baseline visual acuity score, smaller baseline CNV lesion size and younger baseline age were associated with a greater gain of letters with ranibizumab treatment and less loss of letters with PDT.
The authors conclude that subgroup analysis of 12-month data from the ANCHOR study showed ranibizumab to be superior to PDT in all subgroups evaluated. They also conclude that this is consistent with the phase 3 MARINA study of ranibizumab in showing that the most important predictors of visual acuity outcomes were, in decreasing order of impact, the patient’s baseline visual acuity score, CNV lesion size and age.
Souza et al. evaluated the long-term efficacy of IOP reduction and complications of Ahmed glaucoma valve implantation.
The study included 64 patients (78 eyes) with refractory glaucoma who underwent Ahmed glaucoma valve (AGV) implantation with a minimum of three years of follow-up. The primary outcome measure was cumulative probability of success, defined as IOP of less than 21 mmHg and of at least 5 mmHg with a minimum of 15 percent reduction from baseline IOP, without additional glaucoma surgery or loss of light perception. Secondary outcomes included IOP and number of medications at various times after surgery, surgical complications and final visual acuity.
The cumulative probability of success was 80 percent at one year and 49 percent at five years. IOP was reduced from a mean of 30.4 mmHg at baseline to 17 mmHg at 12 months and 15.9 mmHg at 60 months. The number of medications decreased from 3.2 medications at baseline to 1.6 at 12 months and 2.1 at 60 months. Prior glaucoma surgery and the silicone type of AGV were statistically significant risk factors for failure. Archives of Ophthalmology
Archives of Ophthalmology
Mandal et al. evaluated the visual and anatomical outcomes and safety of intravitreal bevacizumab in patients with subfoveal idiopathic choroidal neovascularization (ICNV).
Thirty-two eyes of 32 patients with ICNV received intravitreal bevacizumab (1.25 mg/0.05 ml) in a prospective, interventional study. Intravitreal bevacizumab injection was repeated if optical coherence tomography showed intraretinal edema, subretinal fluid and/or pigment epithelial detachment at four weeks. Ophthalmic evaluations included BCVA, OCT and fundus fluorescein angiography.
Patients were followed for at least 12 weeks. The patients received a mean of 1.7 injections per eye. At 12 weeks, the mean BCVA improved from 20/133 (median, 20/200) to 20/50 (median, 20/40) (P < 0.001). Mean central macular thickness decreased from 314.37 µm at baseline to 236.8 µm (P < 0.001) at 12 weeks. At 12 weeks, 19 eyes (59 percent) had an improvement of BCVA of three lines or more, 11 eyes (34 percent) remained stable and two eyes (6 percent) lost three or more lines. Only one patient developed mild iridocyclitis on the day after first injection, and it resolved with topical prednisolone acetate for one week. No other significant ocular or systemic side effects were observed.
The authors conclude that intravitreal bevacizumab is safe and well tolerated in ICNV for short-term periods. Many patients showed marked improvement in visual acuity and a decrease in central macular thickness.
In this study, Rabinowitz et al. used semiautomated analysis of retinal vessel diameter from digital retinal images of preterm infants at high risk for retinopathy of prematurity to determine whether vessel diameter early in the course of ROP screening helped to predict subsequent progression to severe ROP.
Seventy-eight eyes of 39 patients were photographed during early ROP examinations before 34 weeks gestational age. The diameters of the major temporal retinal arteries and veins were measured in a masked fashion using Vessel Map semiautomated software. Eyes were then grouped by the ultimate maximal severity of ROP seen.
Eighteen eyes of nine patients developed severe ROP requiring laser treatment. Maximal ROP was seen at an average of 2.4 weeks after the photographs of those eyes. The remaining 50 eyes did not develop ROP or developed mild ROP, which did not require treatment by standard clinical guidelines. Comparison of average vessel diameters between groups showed significantly larger average diameters in the eyes that later developed severe ROP and required treatment, compared with those that did not develop ROP or had only mild ROP, which did not require treatment.
The authors performed multivariate analysis adjusting for birth weight, gestational age and chronological age at the time of the photographs, without any reduction in the statistical significance.
They conclude that retinal vessel diameter before 34 weeks gestational age is correlated with the severity of ROP occurring several weeks later. While some overlapping values were observed in individual patients, retinal vessel and retinal vein diameter may be clinically useful in predicting the ultimate severity of ROP.
Sawada et al. measured the concentrations of VEGF in the aqueous humor before and after intravitreal injection of bevacizumab in eyes with proliferative diabetic retinopathy.
Bevacizumab was injected into the vitreous cavity as preoperative adjunctive therapy one week before pars plana vitrectomy to treat proliferative diabetic retinopathy in 18 eyes in 18 patients. Aqueous humor samples were obtained just before intravitreal injection of bevacizumab and just before vitrectomy one week after the injection. VEGF concentration in the aqueous humor was measured using an enzyme-linked immuno- sorbent assay.
VEGF concentration in the aqueous humor ranged from 146 to 676 pg/ml before intravitreal injection of bevacizumab and decreased to less than 31 pg/ml, the lower limit of the enzyme-linked immunosorbent assay (P < 0.001), in all eyes one week after injection. There were no adverse events.
Bashshur et al. studied the efficacy and safety of intravitreal bevacizumab in the management of neovascular age-related macular degeneration when compared with verteporfin photodynamic therapy.
Sixty-four eyes of 64 patients with subfoveal predominantly classic choroidal neovascular membrane were randomized (1 to 1 ratio) to receive intravitreal injections of bevacizumab (2.5 mg/0.1 ml) or standard PDT. BCVA, central retinal thickness and greatest linear dimension of the CNV were compared between both groups at baseline and at three and six months. The decision to re-treat in the PDT group was based on the presence of leakage on fluorescein angiography, while in the bevacizumab group, the decision to re-treat was based mostly on the appearance of subretinal fluid or cystic maculopathy on optical coherence tomography.
Thirty-two patients in the bevacizumab group and 30 patients in the PDT group completed the six months of follow-up. There was no statistically significant difference between the two groups with respect to mean baseline visual acuity, central retinal thickness and greatest linear dimension of the CNV. By the third month, central retinal thickness was significantly better in the bevacizumab group. On the other hand, visual acuity and greatest linear dimension in the bevacizumab group did not show significant improvement compared with the PDT group until six months.
At the conclusion of the study, all eyes in the bevacizumab group and 73 percent of eyes in the PDT group avoided losing three lines of visual acuity. Fifty percent of eyes in the bevacizumab group gained three or more lines of visual acuity vs. 16.7 percent of eyes in the PDT group. Over the six months of the study, the PDT group received an average of 2.3 treatments while the bevacizumab group required an average of 2.4 injections. No systemic or ocular complications were noted in either group.
Mittal et al. reported 14 patients with unilateral (n = 9) or bilateral (n = 5) optic nerve inflammation associated with chikungunya virus infection.
Eight eyes (42 percent) had papillitis, four eyes (21 percent) had retrobulbar neuritis, four eyes (21 percent) had retrochiasmal (optic tract) neuritis and three eyes (16 percent) had neuroretinitis. Parenteral steroids were administered to all patients. Color vision, visual fields and BCVA of 6/12 (or 20/40 Snellen visual acuity) or better improved by the end of three weeks (P < 0.001). Partial to complete recovery of visual function was seen in 10 patients (71 percent).
The authors conclude that acute-onset visual loss due to optic neuritis may be associated with chikungunya virus infection. Corticosteroids accelerated visual recovery, especially when the therapy was initiated at an early stage of the disease.
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
Papadopoulos et al. undertook a prospective study to better understand the incidence, detection patterns, current management and IOP of children 16 and younger in the United Kingdom and the Republic of Ireland with a diagnosis of primary or secondary glaucoma. Consultant ophthalmologists identified 99 children with glaucoma (47 with primary glaucoma and 52 with secondary) diagnosed between December 2001 and November 2002.
The annual incidence of diagnosis of primary congenital glaucoma was 5.41 in 100,000 in Great Britain and 3.31 in 100,000 in the Republic of Ireland—a figure comparable to similar Western countries.
However, the incidence of primary congenital glaucoma in children of Pakistani origin was almost nine times that of Caucasians. In terms of treatment, primary glaucoma was more likely to be treated earlier and with surgery, while more secondary glaucoma cases were managed medically before surgery and with a greater number of topical medications. Sixty percent of children with primary glaucoma and 28 percent with secondary glaucoma achieved IOP control at one year without additional medication.
It is one thing to discover a strong association between age-related macular degeneration and genetic variants. Indeed, many studies have confirmed a strong association between AMD and variants at 10q26. However, it is quite another to identify the causal variants in the region and the possible mechanisms through which these variants influence disease susceptibility. In this study, Kanda et al. identified one single nucleotide polymorphism (rs1049-0924) that alone can account for the association of the 200-kb region at chromosome 10q26 with susceptibility to AMD. To place this finding in perspective, the complement factor H gene at 1q32 requires multiple single nucleotide polymorphisms to explain the association signal.
In making this discovery, the researchers undertook a detailed association analysis of single nucleotide polymorphisms at 10q26. They found that the human retina and various cell lines detect LOC387715/ARMS2 mRNA and then encode a 12-kDa protein, which localizes to the mitochondrial outer membrane when expressed in mammalian cells. From this finding, they propose that rs1049-0924 is a major susceptibility variant for AMD at 10q26. They add that other variants could possibly exist in the region but identifying them would require a very large sample size.
While the cornea has the distinction of being the most densely innervated tissue in the human body, actually assessing changes in corneal innervation density and morphology has been challenging given both the limited availability of healthy corneal tissue for ex vivo study and the rapid pace of corneal nerve degeneration after death. Seeking a better method of measuring these changes, Niederer et al. utilized laser scanning in vivo confocal microscopy technology to study corneal keratocyte and innervation density.
The researchers conducted a cross-sectional study of 85 normal, healthy individuals with a mean age of 38 and a range of ages from 18 to 87. Through laser scanning in vivo confocal microscopy, they found that corneal sub- basal nerve fiber density significantly decreased with increasing age (0.9 percent per year). Also anterior keratocyte density declined by 0.9 percent per year, posterior keratocyte density declined by 0.3 percent per year and endothelial cell density declined by 0.5 percent per year.
They conclude that this relatively linear reduction in corneal innervation, keratocytes and endothelial cell density could possibly have key implications for corneal structure and function.
Optical coherence tomography image artifacts may occur in patients with retinal pigment epithelium detachment and retinal laser scars, leading to possible misdiagnoses. In this study, Karam et al. present software-related artifacts caused by some pigment retinal pathologies. They selected 13 eyes of 11 patients for the study. Ten eyes had retinal pigment epithelial detachment and three had retinal laser scars. The authors reviewed their OCT retinal scans.
When scan protocol analyses were applied, 10 eyes of eight patients with retinal pigment epithelial detachments displayed retinal pigment epithelium flattening and an apparent inversion of the dome of the detachment. In addition, the three eyes with retinal laser scars showed thinning of the retinal pigment epithelium without changes behind the scar.
The investigators conclude with an alert to clinicians: Given the potential for artifacts, OCT results that seem to contradict initial clinical findings should be followed up with a clinical fundus examination.
Roundup of Other Journals is written by Lori Baker Schena and edited by Deepak P. Edward, MD.