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November’s American Journal of Ophthalmology:
September’s Archives of Ophthalmology:
Roundup of Other Journals:
Trabeculectomy Shows No Effect on IOP in Untreated Fellow Eye
Previous reports in the literature have demonstrated a contralateral effect on IOP with the use of unilateral topical antiglaucoma medications. Does the same hold true for unilateral trabeculectomy?
Analyzing data from the Collaborative Initial Glaucoma Treatment Study, Radcliffe et al. looked at 300 patients with newly diagnosed open-angle glaucoma randomized to trabeculectomy as initial therapy. No eyes included in the analysis had had previous trabeculectomy, argon laser trabeculoplasty or cataract extraction. The authors found that the fellow eyes of patients who underwent unilateral trabeculectomy experienced a small decrease in IOP over a 24-month time period. This decrease was modest and only became statistically significant at the 12-month time point.
They conclude that this research—the largest study to date of fellow eye response after trabeculectomy—does not provide evidence of the ophthalmotonic consensual reaction of this procedure and suggests that any effect, if present, is transient and would not likely influence clinical management. Finally, they note that trabeculectomy does not appear to increase the mean IOP in the fellow eye.
Ranibizumab Treat-and-Extend Regimen for AMD
A treat-and-extend regimen (TER) using ranibizumab for age-related macular degeneration was first introduced to minimize the number of intravitreal injections, office visits and ancillary tests. TER begins with monthly injections until signs of resolving exudation are seen on OCT. Re-treatment interval is lengthened by one to two weeks as long as no sign of recurrent exudation appears. When recurrent exudation is detected during follow-up, the treatment interval is reduced to the prior interval. Treatment is given at every visit, but the time between visits is individually tailored based on each patient’s response to treatment.
Gupta et al. conducted a retrospective study of 92 patients and found TER with ranibizumab demonstrated favorable visual acuity results in patients with AMD with significantly fewer visits and intravitreal injections compared with treatment in a fixed, monthly fashion. It also resulted in lower associated direct medical costs compared with some trials using fixed monthly protocols.
While these results point to the possible benefits of TER, the authors caution that their findings should be placed into perspective given the limitations of a retrospective study design of unmasked participants and nonprotocol visions.
Müller’s Muscle Part of the Peribulbar Smooth Muscle Network
Kakizaki et al. have found that Müller’s supratarsal sympathetic muscle has a medial extension and a lateral extension to the peribulbar smooth muscle network, indicating that Müller’s muscle is not an independent structure in the upper eyelid but rather a component of the peribulbar smooth muscle network.
The authors analyzed 20 postmortem orbits (10 right and 10 left) of 15 Asians (eight males and seven females) aged 61 to 93 years at the time of death. The orbits, which were fixed in 10 percent buffered formalin, were studied bilaterally (10 orbits) and unilaterally (10 orbits). The authors showed that the medial extension continued to the medial rectus muscle pulley. The lateral extension reached the lateral rectus muscle pulley by passing through the lacrimal gland fascia of the palpebral lobe—and in some instances also directly continuing to the lateral rectus muscle pulley.
American Journal of Ophthalmology
New Pathogens Identified in Patients With Uveitis
DeGroot et al. analyzed the intraocular fluid in patients with uveitis of unknown origin in a case-control study.
The authors assessed ocular fluids from 139 patients suspected of infectious uveitis for the presence of 18 viruses and three bacteria using real-time polymerase chain reaction (PCR). The ocular fluids from 48 patients with uveitis of known etiology or with cataract were included as controls.
Positive PCR results were found for Epstein-Barr virus, rubella virus and human herpesvirus in one patient and for human parechovirus in four patients. Of the human parechovirus–positive patients, one was immunocompromised and had panuveitis. The other three patients were immunocompetent and had anterior uveitis, all with corneal involvement.
PDT for Macular Circumscribed Choroidal Hemangioma
In a retrospective, consecutive, noncomparative case series, Zhang et al. evaluated the efficacy and safety of photodynamic therapy (PDT) for macular circumscribed choroidal hemangioma in Chinese patients.
Twenty-five eyes with macular circumscribed choroidal hemangioma and vision impairment attributable to subfoveal fluid and retinal detachment underwent visual acuity testing, fundus fluorescein angiography, ultrasonography and OCT examination to evaluate the efficacy and safety of PDT treatment. PDT was performed with a standard concentration of verteporfin and intravenous injection time. Laser was used at 50 J/cm2 for 83 seconds on subfoveal lesions and at 75 J/cm2 for 125 seconds on perifoveal lesions. More than one spot was used for large lesions and spots overlapped only outside the fovea.
The mean follow-up time was 35.5 months. All patients were treated with one session except in two subfoveal cases. The mean BCVA increased from 0.09 to 0.31, and 11 patients (44 percent) had their vision improve by over four lines. The remaining 14 patients (56 percent) had stabilized vision with the retina reattached. The mean thickness of the hemangioma before the treatment was 3.2 mm, and it decreased to 1.3 mm after treatment, with complete regression of tumor in seven cases (28 percent).
PDT with individualized laser parameters for macular circumscribed choroidal hemangioma seems effective and safe, leading to improved or stabilized BCVA as a result of tumor shrinkage and the resolution of the subretinal fluid.
Visual Performance With Monofocal, Accommodating and Multifocal IOLs
In this prospective, nonrandomized clinical trial, Mesci et al. compared the visual performance of patients with unilateral cataract following implantation of monofocal, accommodating, refractive multifocal and diffractive multifocal IOLs.
Eighty-seven patients with unilateral cataract were enrolled in four groups for phacoemulsification and IOL implantation. Twenty-four patients had monofocal IOL implantation (Alcon AcrySof) (group 1), 21 patients had accommodating lenses (Human Optics 1CU) (group 2), 22 patients had diffractive multifocal lenses (Tecnis ZM900) (group 3) and 20 patients had refractive multifocal lenses (AMO ReZoom) (group 4). Ages of patients were between 40 and 70. Parameters analyzed at postoperative month 18 were subjective refractions, monocular and binocular distance, intermediate and near uncorrected visual acuities, monocular distance and near BCVAs, monocular distance-corrected intermediate and near visual acuities, stereopsis, visual complaint and spectacle dependency.
No significant difference was observed between distance and near BCVAs of IOL groups and between intermediate visual acuities of groups 2, 3 and 4. Groups 3 and 4 had near vision that was statistically better than the other groups. No significant difference was observed between near visual acuities of groups 3 and 4. The number of patients with better stereoscopic function, greater spectacle independence and fewer complaints of halo in groups 3 and 4 was significantly higher than in other groups.
Multifocal IOLs seem to provide better stereopsis, higher spectacle independence rates and satisfactory functional vision over a broad range of distances in presbyopic patients with unilateral cataract compared with monofocal and accommodating IOLs.
Keratocyte Density After LASEK With Mitomycin C
In a comparative case series, Benito-Llopis et al. evaluated the effects of laser-assisted subepithelial keratectomy (LASEK) with mitomycin C on keratocyte densities.
Fifty-six eyes were included in the study. The authors compared 28 eyes treated with LASEK with intraoperative 0.02 percent mitomycin C for myopic correction with 28 nontreated eyes. Keratocyte density was measured three months after the surgery in the anterior, middle and posterior stroma and was compared with the corresponding layers in the control eyes.
The anterior layer in the LASEK group was compared with two layers in the control group—the most anterior stromal layer and the 80 µm–deep layer—because that was the mean ablation depth performed in eyes that underwent LASEK.
The authors found a significantly lower keratocyte population in the most anterior stromal layer after LASEK with mitomycin C compared with both the most anterior stromal layer and the 80 µm–deep layer in controls. On the contrary, the treated group showed a significantly higher keratocyte density in both the middle stroma and the deep stroma. The comparison between the average densities through the entire cornea showed a significantly higher keratocyte population in the LASEK with mitomycin C group.
LASEK with mitomycin C seems to cause a decrease in the anterior stromal cell counts three months after the surgery compared with nonoperated corneas. There seems to be a compensating proliferation of keratocytes in the deeper corneal layers, suggesting that the ability of keratocytes to repopulate the cornea is maintained after the surgical procedure.
Archives of Ophthalmology
Fine-Needle Biopsies of Choroidal Melanoma
McCannel et al. identified potentially key genes that were differentially expressed in choroidal melanomas characterized by monosomy 3 and those characterized by chromosome 6p gain without monosomy 3.
The authors obtained material from 31 choroidal melanoma fine-needle aspiration biopsies that met rigorous cytopathologic and nucleic acid integrity criteria. Samples were analyzed by clustering cytogenetic aberrations, sorting by chromosome 3 loss and chromosome 6p gain without chromosome 3 loss, and comparing gene expression profiles. Among the genes identified in the report were tumor necrosis factor receptor superfamily member 19, which was highly overexpressed in chromosome 3 loss tumors, and hedgehog acyltransferase-like (HHATL), which was significantly underexpressed in chromosome 3 loss tumors. HHATL underexpression may represent an early expressional alteration in metastatic choroidal melanoma, given its location on chromosome 3.
The authors conclude that molecular analysis of choroidal melanoma fine-needle biopsies demonstrated two cytogenetically distinct groups characterized by chromosome 3 loss or chromosome 6p gain. Integrative RNA analysis revealed genes with over- and underexpression and identified genes that have not been described by previous studies.
Keratoconus Susceptibility Locus on Chromosome 14
Utilizing a single-nucleotide polymorphism microarray method, Liskova et al. sought to identify genetic factors that could increase susceptibility to keratoconus.
A multiethnic panel of six families with three to five members affected by keratoconus was used, and a whole- genome linkage analysis was performed. From the data generated, linkage analysis results indicated a potential locus for keratoconus on chromosome 14q24.3. Subsequently, candidate gene screening was performed by direct sequencing.
The 14q24.3 region contains a relatively small number of genes of interest, including VSX2, a homeobox gene known to be involved in eye development and implicated in a wide spectrum of ocular disorders. However, sequencing the coding region of VSX2 did not reveal any sequence variants that segregated with disease phenotype in any of these families.
The authors conclude that important inheritable genetic factors that may affect susceptibility to keratoconus are located at locus 14q24.3.
Vascular Tumors of the Iris
Shields et al. reported their experience with iris vascular tumors and related lesions in 54 eyes of 45 patients who were evaluated in the oncology service of Wills Eye Institute.
The tumors were classified as racemose hemangioma, cavernous hemangioma, capillary hemangioma, varix and microhemangiomatosis. Racemose hemangioma and varix and microhemangiomatosis occurred mostly in adults at median age 55 years or older, whereas capillary hemangioma occurred in infancy and cavernous hemangioma with systemic involvement occurred in a child.
Of the 41 eyes with iris racemose hemangioma, none showed systemic involvement. Of all 54 eyes, transient hyphema was the main complication— found at some point in 30 percent or more of each affected eye except for iris capillary and racemose hemangioma, which did not cause hyphema. Surgical resection was performed on one cavernous hemangioma and one varix. The remainder was managed with observation.
The authors conclude that although the existence of iris vascular tumors was once challenged, there are now well-documented examples of iris racemose hemangioma, cavernous hemangioma, capillary hemangioma, varix and microhemangiomatosis. Transient hyphema is the main complication. Observation is usually advised. Most are solitary lesions confined to the iris, and some (cavernous hemangioma and microhemangiomatosis) can have important systemic associations.
Incidence and Outcomes of Herpes Virus Eye Disease
Baratz et al. performed a retrospective review of Olmsted County, Minn., residents with herpes simplex virus eye disease in order to estimate trends in the incidence of herpes simplex virus and to investigate the impact of prophylactic oral antiviral therapy.
The study identified 394 patients diagnosed with herpes simplex virus from 1976 through 2007 for an incidence of 11.8 new cases per 100,000 people per year. The researchers identified no trend in the incidence during the study period. Patients treated with oral antiviral medication were 9.4 times less likely to have a recurrence of epithelial keratitis, 8.4 times less likely to have a recurrence of stromal keratitis and 34.5 times more likely to have a recurrence of blepharitis.
In comparison to results from the Herpetic Eye Disease Study, the efficacy of oral antiviral medication was more profound in preventing recurrence of herpes simplex virus eye 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
Challenges Posed by Comparative-Effectiveness Research
The New England Journal of Medicine
A commentary by Martin et al. in the “Perspective” section of The New England Journal of Medicine draws upon the authors’ experience with the clinical trial comparing ranibizumab (Lucentis) with intravitreal bevacizumab (Avastin) to shed light on the challenges posed by comparative-effectiveness research.
The authors recount the roadblocks as they planned the Comparison of Age-Related Macular Degeneration Treatment Trials (CATT). Cost became an issue when the NEI approved funding for CATT in June 2006: ranibizumab, which was approved by the FDA on June 30, 2006, cost $2,000 for a monthly dose, while intravitreal bevacizumab, which was used off-label to treat AMD, cost $50 a dose.
In clinical trials where there is no pharmaceutical company sponsor or partner, the major question becomes who pays for the drugs being studied. The authors describe the issues dealing with funding provided by Medicare, NIH grants and private health insurance companies, which led to problems with masking. Eventually, the authors dealt with these roadblocks, which delayed the trial for more than a year, and they met their enrollment goal of 1,200 patients in December 2009.
The authors call for a comprehensive federal policy that would cover all drug-related costs and avert the need to rely on current billing and payment mechanisms.
Macular Edema’s Effect on OCT Signal Strength
Hosseini et al. have found that macular edema decreases the signal strength on the Stratus OCT.
For the first part of this study, the authors performed macular OCT in 57 eyes with macular edema at two different times with different degrees of macular edema. They looked at the relationships between signal strength change and change in center point thickness and total macular volume between the two scans. They found that an increase in retinal thickness resulted in a significant decrease in signal strength. The magnitude of this decrease paralleled central retinal thickness and total retinal volume.
For the second part of the study, they performed OCT examinations with macular thickness mapping and retinal nerve fiber layer analysis protocols on 54 eyes with macular edema. They compared the paired signal strength values of the two scan protocols and looked at the relationship between the signal strength differences between the two test protocols with center point thickness and total macular volume.
The authors found that in patients with macular edema, signal strength obtained during macular OCT was significantly lower than that obtained during RNFL OCT examination.
High-Resolution OCT to Study Optic Pit Maculopathy
In this study, Imamura et al. used high-resolution OCT to explore retinal manifestations of optic pit maculopathy.
Participants included 16 patients diagnosed with optic pit maculopathy with a mean age of 35.9 years and visual acuity that ranged from 20/20 to 20/1000. The authors found that fluid seemingly originating from the optic nerve pit extended directly into various layers of the retina. Intraretinal fluid was identified in the outer nuclear layer in 15 eyes (94 percent), the inner nuclear layer in 13 eyes (81 percent), the ganglion cell layer in seven eyes (44 percent) and in the subinternal limiting membrane space in two eyes (13 percent). Of the 11 eyes with retinal detachment, only three appeared to have an outer layer hole. The authors point out that fluid can migrate from the optic nerve pit region into different retinal layers. The fluid enters into these layers and accumulates, resulting in the appearance on OCT of maculopathy.
Roundup of Other Journals is written by Lori Baker Schena and edited by Deepak P. Edward, MD.