October's Ophthalmology:
October's American Journal of Ophthalmology:
August's Archives of Ophthalmology:
Roundup of Other Journals:
Ophthalmology
CAT-152 in Preventing Trabeculectomy Failure
October’s Ophthalmology
CAT-152 (lerdelimumab) is a monoclonal IgG4 antibody that specifically and potently neutralizes human transforming growth factor-beta 2 and has been designed for potential therapeutic use as a scarring inhibitor.
In this phase 3 trial by the CAT-152 0102 Trabeculectomy Study Group involving patients receiving first- time trabeculectomy for intractable glaucoma, researchers administered CAT-152 as an adjunctive treatment to delay or prevent scarring at the bleb site. Participants received subconjunctival injections of CAT-152 or placebo immediately before trabeculectomy, immediately after trabeculectomy, on postop day one and at one week after surgery. The primary outcome measure was treatment success in the study eye at the six- and 12-month follow-up; secondary outcome measures included surgical success, time to surgical failure, IOP and bleb site anatomy. Results showed no difference between CAT-152 and placebo on all outcome measures.
The authors conclude that perhaps a different regimen to neutralize transforming growth factor may be able to improve the prognosis of glaucoma filtration surgery.
Hyaloideocapsular Block Syndrome in an Aphakic Patient
October’s Ophthalmology
A study by Fournie et al. evaluated capsule-related fluid accumulation in an aphakic patient.
The 80-year-old woman presented with a myopic shift and decreased visual acuity in her left eye 16 years after extracapsular cataract extraction without IOL implantation. A milky fluid had accumulated between the posterior lens capsule and the anterior hyaloid. The authors named the condition hyaloideocapsular block syndrome because of its clinical similarities to capsular block syndrome. The patient underwent an Nd:YAG laser hyaloidotomy on the anterior hyaloid membrane, allowing the trapped fluid to flow into the vitreous cavity. The myopic shift immediately disappeared and visual acuity improved.
The authors conclude that this treatment is an effective procedure for hyaloideocapsular block syndrome in the absence of an IOL. In addition, it may be preferable to preserve the capsule if possible, allowing the liquid material to disperse into the vitreous instead of the anterior chamber.
Intravitreal Bevacizumab for Diabetic Macular Edema
October’s Ophthalmology
In a short-term phase 2 study conducted by the Diabetic Retinopathy Clinical Research Network, 121 patients (121 eyes) with DME were randomized to intravitreal bevacizumab either alone or in combination with focal photocoagulation.
The authors observed that while about half the eyes demonstrated an initial positive response to intravitreal bevacizumab exceeding an 11 percent reduction in retinal thickness compared with baseline at either the three-week or six-week visit, the response was similar in the laser group after more than three weeks. In addition, the magnitude of the response was not large for most of the patients.
The authors caution that since this study was designed to help develop a phase 3 randomized trial protocol, the follow-up period and modest sample size yielded limited safety and effectiveness conclusions.
Adverse Effects of Intravitreal Triamcinolone in Patients With Uveitis
October’s Ophthalmology
Galor et al. conducted a retrospective, observational case review to determine whether uveitis patients undergoing macular edema treatment were predisposed to higher complication rates from intravitreal triamcinolone acetonide (IVTA).
The researchers specifically focused on whether a rise in IOP and progression of posterior subcapsular cataract occurred more frequently in patients with uveitis in contrast to individuals with macular edema secondary to other etiologies. Uveitis patients were younger, more likely to be female and more likely to have undergone prior posterior sub-Tenon’s steroid injection and/or glaucoma therapy than those without uveitis. A multivariate analysis indicated that the presence of uveitis constituted the strongest risk factor for an adverse IOP event. In addition, the odds of a documented increase in posterior subcapsular cataract after IVTA injection was 5.6 times greater in uveitis eyes.
The authors recommend counseling patients about the risks associated with uveitis and IVTA, and call for a randomized, long-term controlled study to confirm the benefits of IVTA for macular edema.
IOP Strong Risk Factor, Questionable Predictor of Glaucoma
October’s Ophthalmology
A study by Nemesure et al. evaluated the role of baseline intraocular pressure as a risk factor for incident open-angle glaucoma (OAG) in individuals of African descent who participated in the Barbados Eye Studies.
Two key findings emerged: the study confirmed the role of IOP as an influential risk factor yet also found that IOP had limitations as a predictor of risk. The nine-year cohort study involved 3,222 participants who did not show signs of glaucoma during a baseline examination. After nine years, the incidence of OAG was 1.8 percent among individuals with a baseline IOP of less than 17 mmHg, compared with 22.3 percent among individuals with a baseline IOP of greater than 25 mmHg, for a 13-fold adjusted risk ratio. Yet, most cases arose with an IOP between 17 and 25—more than half had a baseline IOP of less than 21 mmHg.
In conclusion, while the relationship between high IOP and incident OAG remains strong, IOP appears to have limitations in terms of predicting risk.
American Journal of Ophthalmology
Treatment of Bilateral Refractive Amblyopia
October’s AJO
The Pediatric Eye Disease Investigator Group evaluated the amount and time course of binocular visual acuity improvement during treatment of bilateral refractive amblyopia in children between the ages of 3 and 10.
One hundred and thirteen children with previously untreated bilateral refractive amblyopia were enrolled at 27 community- and university-based sites and given optimal spectacle correction. Bilateral refractive amblyopia was defined as 20/40 to 20/400 BCVA in the presence of 4 D or more of hypermetropia by spherical equivalent, 2 D or more of astigmatism, or both in each eye. Best-corrected binocular and monocular visual acuities were measured at baseline and at five, 13, 26 and 52 weeks.
Mean binocular visual acuity improved from 0.5 logMAR units (20/63) at baseline to 0.11 logMAR units (20/25) at one year. Mean improvement at one year for the 84 children with baseline binocular acuity of 20/40 to 20/80 was 3.4 lines, while improvement for the 16 children with baseline binocular acuity of 20/100 to 20/320 was 6.3 lines. The cumulative probability of binocular visual acuity of 20/25 or better was 21 percent at five weeks, 46 percent at 13 weeks, 59 percent at 26 weeks and 74 percent at 52 weeks.
Risk Factors for Cataract in Juvenile Idiopathic Arthritis–Associated Uveitis
October’s AJO
Sijssens et al. sought to identify the risk factors for the development of a cataract requiring surgery in children with juvenile idiopathic arthritis (JIA)–associated uveitis.
Data of 53 children with JIA-associated uveitis, of whom 27 had undergone cataract extraction, were reviewed in this study. The interval between the onset of uveitis and the first cataract surgery was examined in relation to clinical and ophthalmologic characteristics as well as treatment strategies prior to cataract extraction.
A shorter interval between uveitis and cataract surgery was found for children with posterior synechia (vs. those without posterior synechia). No significant difference was found for children in whom the uveitis was the first manifestation of JIA (vs. those in whom arthritis was the first manifestation of JIA) or for children treated with periocular corticosteroid injections (vs. those not treated with periocular corticosteroid injections). Children treated with methotrexate had a longer uveitis-to-cataract-surgery interval than children not treated with methotrexate.
The most significant risk factor for development of an early cataract requiring surgery in children with JIA-associated uveitis was the presence of posterior synechia at the time of the diagnosis of uveitis. However, early treatment with methotrexate was associated with a mean delay of 3.5 years in the development of the cataract.
Microbiology of Pediatric Orbital Cellulitis
October’s AJO
McKinley et al. evaluated the microbiology of pediatric orbital cellulitis associated with sinusitis using a retrospective review of medical records.
All cases of pediatric patients treated for orbital cellulitis associated with sinusitis at Texas Children’s Hospital between December 2001 and September 2005 were reviewed. Thirty-eight cases were identified. Fifteen received medical management alone, whereas 23 patients received a combination of medical and surgical intervention. Three patients had multiple surgical procedures performed. Of the procedures performed, four were sinus irrigation, 12 were sinusotomy and drainage, nine were orbitotomy with drainage of abscess, and one was craniotomy with drainage of abscess. Surgical aspirate specimens yielded a higher positive-culture result rate with nine out of nine orbital abscesses and 13 out of 16 sinus aspirates demonstrating a positive yield. Two of the 27 blood cultures had a positive yield. Staphylococcus species was the most common organism isolated. Methicillin-resistant S. aureus represented 73 percent of S. aureus isolates. Streptococcus species was the next most common pathogen. Three cultures yielded Haemophilus species with one being positive for H. influenzae.
Organisms responsible for pediatric orbital cellulitis are evolving, with Staphylococcus followed by Streptococcus species being the most common pathogens. The occurrence of methicillin-resistant S. aureus in pediatric orbital cellulitis is increasing, and empiric antimicrobial therapy should be directed against these organisms if they are prevalent in the community. Sinus and orbital abscess aspirates yielded the greatest number of positive cultures, though these invasive surgical procedures should be performed only when clinically indicated.
Valacyclovir for the Prevention of Recurrent Herpes Eye Disease
October’s AJO
Miserocchi et al. compared one-year treatment of valacyclovir with acyclovir in preventing recurrence of the herpes simplex virus (HSV) eye disease.
Out of 52 immunocompetent patients with a history of recurrent ocular HSV disease, 26 were randomized to the valacyclovir group (one 500-mg tablet daily) and 26 were randomized to the acyclovir group (one 400-mg tablet twice daily). The recurrence rate of ocular HSV during 12 months of treatment and side effects were monitored. Recurrence of ocular HSV during the 12-month treatment period was 23.1 percent in each group. No difference between the two groups was observed regarding the nature, frequency or severity of adverse events. The most frequent adverse events were nausea and headache. Archives of Ophthalmology
Archives of Ophthalmology
Ablation Diameter, Pupil Size and Visual Function After LASIK
August’s Archives
Controversy regarding the association between pupil diameter and the risk of visual disturbances following LASIK has led to difficulties in patient selection and counseling prior to refractive surgery. In this study, Schmidt et al. used the NEI Refractive Error Quality of Life instrument to evaluate the subjective visual and functional outcome of LASIK surgery in relation to the preoperative measurement of mesopic and scotopic pupil size.
Ninety-seven patients completed the questionnaire, and Spearman correlation coefficients were calculated for the association between refractive error quality- of-life subscale scores and multiple parameters, including pupil diameter. The researchers found that postoperative uncorrected visual function was strongly correlated with patient satisfaction. Larger pupil diameter, however, was not associated with postoperative satisfaction or visual function, thus providing further evidence that pupil diameter is not a reliable predictor of quality of vision following LASIK.
Vision Loss in Patients With Glaucoma Undergoing Trabeculectomy
August’s Archives
In this study, Law et al. evaluated the visual outcomes in patients with advanced visual field loss undergoing trabeculectomy with adjunctive intraoperative mitomycin C application.
The records of 117 patients (117 eyes) were retrospectively reviewed. Using threshold automated perimetry, advanced visual field defects were defined as those with sensitivity of 5 dB or less either in more than 85 percent of test points, excluding the central four test points, or in more than 75 percent of test points, including three of the central four test points.
The authors found that severe loss of central vision occurred in seven (6 percent) of the 117 eyes because of hypotony maculopathy (three cases), uncontrolled elevated IOP (two cases), posterior subcapsular cataract increase (one case) and inflammatory reaction (one case).
Unexplained snuff-out or loss of central vision was not observed. In addition, patients who lost central vision had statistically significant higher preoperative IOPs and higher rates of surgical complications compared with those who did not have severe loss of central vision.
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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.
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| EAGLE-EYED MDS WANTED |
| EyeNet Magazine will be reporting live at the Annual Meeting in New Orleans in its Academy Live e-newsletter. We will need the help of two or three physicians each afternoon to join us in the press room to review brief summaries for medical accuracy. If you expect to have 15 spare minutes at around 5:30 p.m. any day of the meeting except Tuesday, please e-mail Denny Smith at dsmith@aao.org, or call 415-447-0203 by Nov. 1. All guest medical editors will be acknowledged in Academy Live e-mail blasts. |
Roundup of Other Journals
Leber’s Congenital Amaurosis Caused by Mutations in LCA5
Nature Genetics
2007;39:889–895
Hollander et al. demonstrate that the LCA5 gene on chromosome 6q14, which encodes the ciliary protein lebercilin, is associated with Leber’s congenital amaurosis (LCA)—the most common cause of congenital blindness in infants and children.
Their findings highlight the emerging role of disrupted ciliary processes in the molecular pathogenesis of LCA. Using homozygosity mapping, the researchers detected homozygous nonsense and frameshift mutation in LCA5 in five families affected with LCA. The LCA5 transcript was completely absent in a sixth family with the condition. Reverse transcriptase polymerase chain reaction analysis demonstrated that the LCA5 gene is widely expressed in human tissues, including the eye, inner ear, kidney, regions of the central and peripheral neural system, the gut, and the ciliated epithelium of the nasopharynx, trachea and lung. Yet the phenotype in affected individuals is limited to the eye. The researchers found that lebercilin localizes the connecting cilia of photoreceptors to the microtubules, centrioles and primary cilia of cultured mammalian cells. They identified 24 proteins linking lebercilin to centrosomal and ciliary functions.
The authors conclude that the genes encoding the lebercilin interactome should also be considered as candidate genes for LCA and other ciliopathies.
Genetic Role in Peripapillary Atrophy
Investigative Ophthalmology & Visual
Science
2007;48:2529–2534
Peripapillary atrophy type beta (beta-PPA) is a frequent ocular finding known to be associated with both the prevalence and progression of open-angle glaucoma. In addition, the presence of beta-PPA and its enlargement over time have been reported to precede and predict the onset of glaucoma in ocular hypertension.
In a twin study involving 506 female twin pairs between ages 50 and 79, Healey et al. attempted to evaluate the role of genes and environment in beta-PPA. Their findings indicate that the presence of beta-PPA appears to be under strong genetic control, with only a small amount of this genetic effect shared with the genes involved in myopia. Beta-PPA prevalence was 25.1 percent and did not vary with zygosity. The researchers estimated that genetic effects played an important role, with a heritability adjusted for refraction of 70 percent.
While more clarification is needed, the findings from this study raise the possibility of a genetic basis for optic disc morphologic characteristics associated with glaucoma.
Novel Vitreous Substitute for Pars Plana Vitrectomy
Eye
Published online May 25, 2007
The search for a safe and effective artificial vitreous substitute for pars plana vitrectomy surgery remains elusive. However, Gao et al. have developed a nontraditional strategy, devising a capsular artificial vitreous with a pressure-control valve to replace the natural vitreous.
The capsule is folded and implanted into the vitreous cavity through a 1.5-mm scleral incision. Physiological balanced solution is then injected into the capsule through the valve and the pressure is adjusted accordingly. Using a rabbit model, the authors demonstrated that this device could effectively support the retina and did not induce any significant pathological changes during an eight-week period.
They note that their vitreous system had many strengths: It was safe and easy to implant, can be removed, can support the retina by slightly inflating and can alter the IOP through the tube-valve system.
Studies are currently under way to determine the device’s biocompatibility over a longer period of time. Additional research is needed to evaluate its effectiveness in complex vitreoretinal diseases.
Calculating IOL Power After Radial Keratotomy
Journal of Cataract and Refractive Surgery
2007;33:1045–1050
It is inevitable that some patients who underwent radial keratotomy in their younger years are now requiring cataract surgery. Yet calculating IOL power tends to be a challenge; early attempts produce hyperopic results because the central flattening that occurs late after radial keratotomy can render invalid the simulated keratometry taken at a radius of 1.5 mm from the corneal apex in terms of the refractive power of the cornea.
To develop a standardized way to calculate IOL power after radial keratotomy using guidelines generally available to ophthalmologists, Awwad et al. conducted a review of 16 eyes of 14 patients who underwent radial keratotomy and subsequent phacoemulsification and posterior chamber IOL implantation. They found that the most accurate approach for corneal power determination in these patients involved averaging the topographic data of the central 3-mm area, and then applying this method with a double-K Holladay 1 IOL formula.
Since different topography systems may yield different results, the authors urge practitioners to conduct preliminary testing of retrospective data using back-calculation when working with other topography systems.
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Roundup of Other Journals is written by Lori Baker Schena and edited by Deepak P. Edward, MD.
