• Journal Highlights

    A Review of the Literature


    American Journal of Ophthalmology
    JAMA Ophthalmology
    Roundup of Other Journals


    Assessing Retinal and Systemic Toxicity of Intravitreal Melphalan

    September Ophthalmology

    Although intravitreal melphalan has gained acceptance as a treatment for refractory vitreous seeds in retinoblastoma, limited data are available on its retinal and systemic toxicity. Francis et al. assessed toxicity issues in a two-part investigation and found evidence of retinal toxicity but not of systemic toxicity.

    The researchers conducted two studies: a clinical study of 16 retinoblastoma patients and a preclinical study of 12 rabbits. In the human study, 16 eyes received a total of 107 weekly injections of 30 µg of melphalan; the median number of injections per eye was 6.5 (range, 5-8). In the animal study, the rabbits were given three weekly injections of 15 µg of intravitreal melphalan or vehicle in the right eye.

    Complete blood counts were obtained in both studies, and no adverse systemic effects were noted in either study. Electroretinogram (ERG) responses were also recorded. In the humans, ERG testing was performed at baseline, before each injection, and at each follow-up visit. In the rabbits, ERG responses were obtained before and after melphalan injections. Histopathology was also evaluated in the rabbits’ eyes. Using linear regression analysis, the researchers found that for every weekly 30-µg injection of melphalan in humans, the ERG response decreased by about 6 µV. However, once treatment ended, ERG responses remained stable. From these findings, the researchers concluded that 1) the drug appears to have an abrupt impact on retinal function in the initial phase of treatment, 2) the effect is apparently permanent, and 3) the effect does not appear to progress once the treatment course is complete. These results were validated in the rabbit study.


    Aqueous Suppressants and Outcomes of Ahmed Glaucoma Valve Implantation

    September Ophthalmology

    Pakravan et al. evaluated the effect of early postoperative use of aqueous suppressants on outcomes seen with the Ahmed glaucoma valve (AGV). They found that early treatment with these drugs may improve outcomes in terms of intraocular pressure (IOP) reduction, hypertensive phase frequency, and success rate.

    For this randomized clinical trial, the researchers evaluated 94 eyes of 94 patients who had AGV surgery for refractory glaucoma. The patients were evenly divided into two groups: 1) those who received topical timolol-dorzolamide fixed-combination drops twice daily as soon as postsurgical IOP exceeded 10 mmHg, and 2) those who received conventional stepwise treatment when IOP exceeded a target pressure of 15 mmHg.

    Groups 1 and 2 were followed for a mean of 45 ± 11.6 and 47.2 ± 7.4 weeks, respectively. The number of glaucoma medications in the early postoperative period was higher in group 1, but there was no significant difference in the number of medications at six or 12 months.

    The incidence of hypertensive phases was lower in group 1. In addition, IOP was consistently and significantly lower in group 1 at all intervals except at week 54—and even then, IOP was still lower in group 1 than in group 2. All told, these differences amounted to a higher success rate in patients who received early aqueous suppressant treatment (63.2 percent) than in those who received conventional treatment (33.3 percent).

    The researchers cautioned that the relatively young (in their 40s) patients enrolled in this study may have a more intensive healing response than an older age group; and, thus, their results might not be applicable to more typical glaucoma patients.


    Three Years of Dexamethasone Implant for Diabetic Macular Edema

    Published online June 5, 2014

    Boyer et al. evaluated the dexamethasone (DEX) intravitreal implant in patients with diabetic macular edema (DME). They found that up to one-third of patients who received the DEX implant achieved 20/40 vision or better after their first implant—and that the benefit persisted over the long term when cataracts were removed as needed.

    The researchers conducted two randomized masked, sham-controlled trials with identical study protocols; results were pooled for this analysis. A total of 1,048 patients with DME were enrolled; at baseline the patients had best-corrected visual acuity (BCVA) of 20/50 to 20/200 and a central retinal thickness of 300 µm or greater.

    The patients were randomized into three treatment groups: 0.7-mg DEX implant (n = 351), 0.35-mg DEX implant (n = 347), and sham (n = 350). Outcome measures included BCVA, adverse events, and intraocular pressure (IOP).

    At three years, 607 patients had completed the study (0.7 DEX = 225; 0.35 DEX = 230; sham = 152). With regard to visual outcomes, 22.2 percent of the 0.7-mg DEX group gained 15 letters or more compared with 18.4 percent of the 0.35-mg DEX group and 12 percent of the sham group. Rates of cataract-related adverse events in phakic eyes were 67.9 percent, 64.1 percent, and 20.4 percent in the 0.7-mg DEX group, the 0.35-mg DEX group, and the sham group, respectively. Increases in IOP were generally well controlled, though two patients who received DEX implants required glaucoma surgery. Patients who received either of the DEX implants had a greater reduction in central retinal thickness than those in the sham group.

    Finally, the DEX patients received an average of four to five implants during the study. This represents a significant decrease in treatment burden for patients when compared with anti-VEGF injections for DME, the researchers noted.


    Characteristics of Bilateral Lacrimal Gland Disease

    Published online June 4, 2014

    In the largest study of bilateral lacrimal gland (LG) disease to date, Tang et al. characterized the diagnoses, clinical features, and outcomes in a series of patients with the condition. They found that the cause was most often inflammatory, followed by structural and lymphoproliferative etiologies. In addition, they found that despite local control with corticosteroids or radiotherapy, the underlying disease persisted in 71 percent of patients and led to death in 3 percent.

    For this retrospective case series, the authors evaluated 97 patients who were drawn from the practices of oculoplastic specialists and ocular oncologists at 18 institutions in the United States and Australia. The patients ranged in age from 8 to 84 years, and most (77 percent) were female; 49 percent of the patients were black, 38 percent were white, and 12 percent were Hispanic.

    The most common diagnoses were idiopathic orbital inflammation (30 percent), sarcoidosis (20 percent), LG prolapse (15 percent), and lymphoma (11 percent). Inflammatory conditions were more likely in younger patients and in those with pain and mechanical blepharoptosis. Conversely, lymphoma was more likely in older patients who had no signs of active inflammation. Black patients were more likely to have sarcoidosis.

    The authors recommended that history and physical examination take precedence in the initial workup, with serologic analysis and imaging providing supplementary information when warranted. LG biopsy remains the gold standard for histopathologic diagnosis, they said.


    Cost-Effectiveness of Treatments for Vitreomacular Adhesions and Macular Holes

    Published online June 5, 2014

    What is the most cost-effective therapy for vitreomacular adhesions (VMAs) and full-thickness macular holes (MHs)? Chang et al. compared the costs and visual benefits of surgery and pharmacologic vitreolysis with ocriplasmin and found that surgery—specifically, pars plana vitrectomy (PPV)—was the most cost-effective option.

    For this study, the outcomes of published clinical trials were used to generate a Markov model of cost-effectiveness and utility. Outcome measures included costs of therapy and cost per quality-adjusted life year (QALY).

    When PPV was selected as the primary procedure, the overall imputed cost ranged from $5,802 to $7,931, compared with $8,767 to $10,977 for ocriplasmin. Similarly, the cost per QALY ranged from $5,444 to $7,442 for PPV versus $8,159 to $10,244 for ocriplasmin. A third treatment—intravitreal saline injection—also was evaluated, as it was used during a clinical trial of ocriplasmin. The overall imputed cost for this approach ranged from $5,828 to $8,098, and the cost per QALY was $5,458 to $7,583.

    The authors noted that this cost model has limitations, including the lack of an observational arm and the exclusion of additional costs associated with surgery that are difficult to quantify, such as missed work from facedown positioning. In addition, they pointed out that pharmacologic vitreolysis is a relatively new therapy; thus, its long-term effects, which may not be fully understood, could affect the outcome of a later analysis.


    American Journal of Ophthalmology

    Reduction in Mean Deviation Values in Automated Perimetry in Eyes With Multifocal IOLs

    August AJO

    Farid et al. used a prospective, age-matched comparative analysis to evaluate differences in mean deviation (MD) values on automated perimetry in healthy eyes with multifocal versus monofocal intraocular lens (IOL) implants. A significant reduction in MD was found with multifocal IOLs compared with monofocal IOLs.

    A total of 37 healthy eyes in 37 patients with bilateral multifocal (n = 22) or monofocal (n = 15) IOLs were studied. Humphrey Visual Field 10-2 testing was performed on all patients. MD and pattern standard deviation (PSD) numerical values were evaluated and compared between groups. The average MD was –2.84 dB for the multifocal IOL group and –0.97 dB for the monofocal IOL group. There was no significant difference in PSD between the two groups. Eyes that had visual field testing six or more months after IOL placement showed no improvement in MD compared with eyes tested at less than six months.

    The authors concluded that multifocal IOL implants cause significant nonspecific reduction in MD values that does not improve with time or neuroadaptation. They emphasized that clinicians should be cautious in considering multifocal IOLs for eyes that require regular visual field testing, such as those with glaucoma; and for eyes where central visual disease already exists, such as those with macular degeneration.


    Progression of Presbyopia After Laser In Situ Keratomileusis

    August AJO

    Tsuneyoshi et al. assessed the effect of laser in situ keratomileusis (LASIK) on near visual function in presbyopic patients aged 45 years or older in a retrospective cohort study.

    Fifty-three eyes of 40 patients 45 years of age and older who had undergone LASIK for high myopia were included. For each eye, the minimum add power needed to obtain the best-corrected near visual acuity was measured preoperatively and three months postoperatively; and the correlations with the powers corrected by LASIK, corneal higher-order aberrations (HOAs), ocular HOAs, and patient ages were evaluated using univariate and multivariate analysis.

    The mean patient age was 50 ± 4.1 years; the power corrected by LASIK was –7.56 ± 1.06 D. The mean add power was 1.80 ± 0.60 D preoperatively, which increased significantly to 2.18 ± 0.69 D postoperatively. Significant correlations with the increased add powers were detected for age and for the power corrected by LASIK but not for corneal and ocular HOAs. After multivariate analysis, only age correlated significantly. The overall percentage of eyes that required an increase of 0.5 D add or more was 60.4 percent. However, when this result was analyzed by age, 70 percent of patients aged 45 to 49 experienced that increase, compared with 14.3 percent in the 50 to 59 age group.

    The study confirmed the apparent progression of presbyopia after LASIK for high myopia and the importance of obtaining informed consent from patients, especially those with early presbyopia.


    IOP Elevation in Eyes Receiving Intravitreal VEGF Therapy

    August AJO

    Yannuzzi et al. studied the intravitreal anti–vascular endothelial growth factor (VEGF) injection techniques and preferences within the retinal community and identified factors potentially associated with the development of sustained intraocular pressure (IOP) elevation in patients who received injections for neovascular age-related macular degeneration (AMD). Using a cross-sectional physician survey, the authors found that a high-volume, fast-injection technique may be associated with this treatment complication.

    The researchers surveyed 530 retina specialists in both private and academic practices regarding their current intravitreal injection protocols, including the anti-VEGF drug of choice, needle gauge, injection volume, injection technique, and self-reported prevalence of sustained IOP elevation. Multivariate logistic regressions were performed to assess the potential influence of these factors on long-term IOP.

    Among these specialists, 292 (55 percent) reported believing that intravitreal anti-VEGF therapy may cause sustained IOP elevation. When these respondents were queried further on prevalence of this IOP elevation, the most common prevalence was 1 to 2 percent (reported by 48 percent), followed by 3 to 5 percent (reported by 34 percent). There was no relationship between the frequency of sustained IOP elevation and anti-VEGF drug of choice. The strongest association found in the study was with high-volume, fast injections: Physicians who injected more than 0.05 cc in less than 1 second were 5.56 times more likely to observe a high frequency of sustained IOP elevation.

    The authors speculated that the underlying mechanism for this complication might be injury to the trabecular meshwork resulting from rapid elevations in IOP. However, they cautioned that their study—because it is based on a self-reported survey—does not contain purely objective data obtained from the clinical record. Thus, its results must be interpreted critically.


    JAMA Ophthalmology

    Atropine vs. Patching for Treatment of Moderate Amblyopia: Follow-up at 15 Years of Age

    July JAMA Ophthalmology

    Initial treatment of amblyopia with patching of, or atropine sulfate eyedrops in, the fellow eye has been shown to improve visual acuity (VA) in the short term. To investigate the durability of the effect, Repka et al. evaluated VA at 15 years of age among patients who were younger than 7 years when enrolled in the Pediatric Eye Disease Investigator Group (PEDIG) treatment trial for moderate amblyopia. The PEDIG trial randomly assigned 419 children with amblyopia (VA, 20/40-20/100) to patching (minimum of six hours per day) or atropine sulfate eyedrops 1 percent (one drop daily) for six months, with treatment after six months at the discretion of the investigator.

    Two years after initial enrollment, an unselected subgroup of 188 children was enrolled into long-term follow-up. Of these, 147 were examined at 15 years of age. Mean VA in the amblyopic eye measured at that age was approximately 20/25; 60 percent had a VA of 20/25 or better, including 33 percent with 20/20 or better. Mean interocular acuity difference (IOD) was 0.21 logMAR (2.1 lines); 48 percent had an IOD of two or more lines, and 71 percent had one or more lines.

    Better VA was achieved in children who were younger than 5 years at enrollment into the initial trial (mean logMAR, 0.09) compared with those aged 5 to 6 years (mean logMAR, 0.18; p < .001). No significant VA differences were seen between the atropine and patching groups in either the amblyopic eye (p = .44) or the fellow eye (p = .43).

    The authors concluded that, at age 15, most children treated for moderate amblyopia when younger than 7 years have good VA, though mild residual amblyopia is common, and outcomes are similar whether the initial treatment was with atropine or patching. Further, the treatment benefit persists until at least 15 years of age.


    Efficacy and Safety of Antifungal Additives in Optisol-GS Corneal Storage Medium

    July JAMA Ophthalmology

    Optisol-GS, the most common corneal storage medium in the United States, contains antibacterial but no antifungal supplementation. However, most cases of postkeratoplasty endophthalmitis and keratitis are now caused by fungi, most commonly Candida species. Layer et al. performed in vitro studies to assess the efficacy and safety of voriconazole and amphotericin B in reducing Candida contamination of Optisol-GS under normal storage conditions.

    For the efficacy study, the researchers used two sets of 10 vials of Optisol-GS containing different concentrations of voriconazole or amphotericin B, with two unaltered vials of Optisol-GS as controls. Known concentrations of Candida albicans were added to one set of vials, and Candida glabrata to the other set. Growth of C. albicans and C. glabrata was observed in all voriconazole-supplemented vials. In contrast, there was no growth of either organism in amphotericin B–supplemented vials, except at the lowest concentrations on day 2, when viable counts of C. glabrata were reduced by 99 percent and 96 percent, respectively.

    For the safety study, researchers used 15 pairs of research-grade donor corneas, separated them, and randomly placed them into each of the different concentrations of the supplemented or control Optisol-GS. Compared with controls, corneas in supplemented Optisol-GS showed no apparent differences in endothelial cell density reduction, percentage of intact epithelium, or percentage of nonviable endothelial cells, except for those in the solution containing the highest concentration of amphotericin B (10 times minimum inhibitory concentration).

    The authors concluded that the addition of amphotericin B to Optisol-GS may significantly improve activity against contamination with Candida species.


    Ophthalmologic Examinations in Areas of Miyagi Prefecture Affected by the Great East Japan Earthquake

    July JAMA Ophthalmology

    One month after a severe earthquake in Japan in 2011, Doi et al. were granted free use of Bascom Palmer Eye Institute’s Mission Vision Van, a customized bus that was airlifted to Japan. The authors describe their use of this mobile eye clinic to provide ophthalmologic care in the disaster zone in Miyagi Prefecture. 

    They evaluated 731 patients who received treatment in the eye care van between April 15 and May 29, 2011. Of the 914 diagnoses made, 358 were refractive disorders (39.2 percent), which were the most common ocular conditions observed; other diagnoses included 155 cataracts (17 percent), 106 dry eye (11.6 percent), and 73 infectious diseases (8 percent) such as conjunctivitis. Overall, emergency prescriptions included 871 bottles of eyedrops, among which were 222 prescriptions for dry eye (25.5 percent), 189 for cataracts (21.7 percent), and 107 for glaucoma (12.3 percent).    

    The authors had initially expected that ocular infectious diseases might be aggravated by conditions in the disaster area, but they found this to be a relatively minor concern. Instead, a substantial number of patients needed replacements for eyeglasses, contact lenses, and eyedrops lost in the earthquake; and the authors concluded that the mobile clinic appears to be a useful way to provide ophthalmologic examinations and support after a disaster.


    Ophthalmology summaries are written by Jean Shaw and edited by Susan M. MacDonald, MD. American Journal of Ophthalmology summaries are edited by Thomas J. Liesegang, MD. JAMA Ophthalmology summaries are based on authors’ abstracts as edited by senior editor(s).


    Roundup of Other Journals

    Intraoperative Aberrometry During Cataract Surgery

    British Journal of Ophthalmology
    Published online May 30, 2014

    In the first report to address quality and reproducibility of intraoperative wavefront aberrometry (IWA) in a large sample of cataract patients, Huelle et al. found that, at this time, IWA cannot be considered a reliable guide to the surgical refractive plan.

    For this prospective study, the researchers evaluated 74 eyes of 74 consecutive patients. Three cataract surgeons at the same eye hospital in Hamburg, Germany, performed all procedures, using the same equipment, same type of intraocular lens, and standard phacoemulsification technique. IWA refraction (with the Wavefront Supported Custom Ablation device [Zeiss Meditec]) was recorded at seven defined measurement points during surgery.

    Out of 814 intraoperative measurement attempts, 462 wavefront maps could be obtained, yielding a success rate of 56.8 percent. The most successful readings (n = 63) were achieved in aphakia with viscoelastic, and the highest and lowest quality of wavefront maps across all measurement points were obtained after clear corneal incision (50.63 percent) and in pseudophakia with viscoelastic (29.19 percent).

    Factors that may affect the precision and quality of IWA measurements include topical anesthesia and corneal wound hydration, vitreous hydration, a varying effective IOL position, and intraoperative variation in anterior chamber depth, the researchers said. They concluded that more research is needed to improve the reliability of IWA measurements.


    The High Cost of Drugs for AMD

    Published online May 23, 2014

    In a Viewpoint article, Silver took on the contentious issue of the cost of drugs used to treat age-related macular degeneration (AMD). He noted that an intravitreal injection of ranibizumab is 40 times more expensive than one of bevacizumab, while the average sales price per milligram of aflibercept in the ophthalmic drug Eylea is about 100 times that of aflibercept in the anticancer drug Zaltrap. The bottom line: The approved anti-AMD drugs cost Medicare $1 billion to $2 billion per year, or roughly 10 percent of total Medicare part B drug expenditures.

    Currently, the FDA does not consider economic issues when approving drugs, and the author said that, if unchallenged, such patterns of price discrimination may become even more widespread, given the financial benefits for drug companies.

    As a potential solution, the author pointed out that CMS has the flexibility to choose different ways of determining how much it will pay for products if it finds that current payment amounts are “inherently unreasonable.” To date, this rule has been invoked only for medical equipment, he said, noting that CMS now has the opportunity to test its applicability to these costly anti-AMD medications.


    Risk Factors for Acute IOP Rise After Cataract Surgery

    Journal of Cataract and Refractive Surgery

    What factors predispose glaucoma patients to experiencing sharp spikes in intraocular pressure (IOP) after cataract surgery? Slabaugh et al. evaluated this question and found that patients who had longer axial lengths or associated characteristics, were taking a higher number of IOP-lowering medications before cataract surgery, had previously undergone laser trabeculoplasty, or were not given oral acetazolamide following cataract surgery were at greater risk of experiencing an IOP rise.

    This retrospective case series included 271 patients who had been treated by the same surgeon between 1996 and 2012. All told, 45 eyes (17 percent) had a spike of greater than 50 percent above baseline IOP during the immediate postoperative period. All but one of these patients regained IOP control with additional medications; the remaining patient required a trabeculectomy during the 90-day postoperative period.

    No significant differences in race, type of glaucoma, or visual field indices were found between those who had an IOP spike and those who did not. Moreover, no technical intraoperative factor—such as type of incision or choice of IOL—was found to reach statistical significance.


    Roundup of Other Journals is written by Jean Shaw and edited by Deepak P. Edward, MD.

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