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  • Journal Highlights

    A Review of the Literature


    American Journal of Ophthalmology
    JAMA Ophthalmology
    Roundup of Other Journals


    Focal Lamina Cribrosa Defects and Glaucomatous Progression

    Published online April 1, 2014

    Faridi et al. evaluated the association between focal structural defects of the lamina cribrosa (LC) and glaucomatous visual field (VF) progression. They found that VF loss progresses faster in eyes with such defects than in eyes without them.

    For this retrospective observational study, the researchers evaluated 169 patients (169 eyes) with glaucoma. Of the 169 patients, 125 had primary open-angle glaucoma, 20 had exfoliation glaucoma, 11 had pigmentary glaucoma, and 13 had chronic angle-closure glaucoma.

    Enhanced-depth imaging optical coherence tomography (EDI OCT) was used to detect focal LC defects laminar holes or disinsertions with a diameter greater than 100 µm. The edges of these defects were marked in the EDI OCT images, reconstructed three-dimensionally, and superimposed on optic disc photographs.

    All told, 81 eyes had focal LC defects; of these, 38 (47 percent) experienced VF progression. In contrast, 22 of the 88 eyes (25 percent) without LC defects experienced VF progression. In addition, the researchers found that VF deteriorates faster both globally and locally in the eyes with focal LC defects. The mean rate of VF progression was –0.54 ± 0.99 decibels (dB) per year in eyes with LC defects compared with –0.28 ± 0.53 dB per year in eyes without defects.

    Reasons for the increased risk and faster rate of VF progression in eyes with focal LC defects are unclear. The researchers theorized that once a localized area of the LC is damaged, that area may become more vulnerable, initiating a vicious cycle that leads to progressive retinal ganglion cell and VF loss.


    Intravitreal Aflibercept for Macular Edema due to CRVO: Two-Year Results

    Published online March 27, 2014

    Heier et al. evaluated the efficacy and safety of intravitreal aflibercept for the treatment of macular edema secondary to central retinal vein occlusion (CRVO). They found that visual and anatomic improvements peaked at the 24-week mark and were maintained at week 52 but then declined by week 100.

    These two-year results were from the COPERNICUS study, a randomized double-masked phase 3 trial. For the study, 114 patients received intravitreal aflibercept injections every four weeks, while 74 received sham injections up to week 24. From weeks 24 to 52, patients in both arms were evaluated monthly and received intravitreal aflibercept on an as-needed basis (PRN). From weeks 52 to 100, all patients were evaluated at least quarterly and received intravitreal aflibercept PRN.

    The patients who received aflibercept throughout the trial had the greatest gains in visual acuity: At 24 weeks, 56.1 percent had gained 15 or more letters; this dropped slightly to 55.3 percent at week 52, and 49.1 percent at week 100. In comparison, the percentages of patients in the sham/aflibercept arm who gained 15 or more letters were 12.3 percent at week 24, 30.1 percent at week 52, and 23.3 percent at week 100.

    Similarly, the proportion of patients with no retinal fluid decreased after the treatment regimen was changed from fixed dosing to PRN dosing, with further declines when the monitoring frequency was decreased from monthly to at least quarterly.

    The authors commented that these findings are consistent with those of the CRUISE and HORIZON trials that studied ranibizumab treatment in CRVO. Together, the results suggest that long-term dosing with anti-VEGF agents may be necessary to control macular edema in many patients with CRVO—and that PRN dosing with quarterly monitoring may not be the optimal protocol. 


    Intra-Arterial Chemotherapy Effective for Retinoblastoma

    Published online March 24, 2014

    In this five-year analysis of intra-arterial chemotherapy (IAC) for retinoblastoma, Shields et al. stated that the treatment is remarkably effective.

    For this retrospective interventional case series, the researchers evaluated 67 patients (70 eyes). The mean patient age at time of treatment was 30 months (range, 4 months to 33 years). Ocular involvement was unilateral in 42 patients and bilateral in 25. IAC was delivered as primary therapy in 36 eyes and as secondary therapy after previously failed treatments in 34 eyes. Each eye received a mean of three IAC sessions (range, one to seven sessions) with melphalan and, if needed, topotecan and/or carboplatin.

    Globe salvage was achieved in 72 percent of eyes treated with primary IAC and in 62 percent of eyes treated with secondary IAC. Salvage rates were also stratified by International Classification of Retinoblastoma groups B through E (none of the patients were classified as group A) as follows: group B (one patient), 100 percent; group C (four patients total), 100 percent; group D (17 patients total), 94 percent; and group E (14 patients total), 36 percent. Eyes that required enucleation generally demonstrated extensive recurrence of subretinal or vitreous seeds, the researchers said. 


    Prevalence of Color Vision Deficiency by Gender and Ethnicity in Preschool Children

    Published online April 3, 2014

    In the first population-based study to do so, Xie et al. evaluated the prevalence of color vision deficiency (CVD) in preschool children by ethnicity and gender. They found the greatest prevalence of CVD among non-Hispanic white boys and the lowest among girls of all ethnic groups.

    Of the 5,960 children between 30 and 72 months of age who were recruited for this population-based cross-sectional study, 4,177 were able to complete color vision testing. They were from four racial/ethnic groups— black, Asian, Hispanic, and non-Hispanic white—and lived in Southern California.

    A total of 63 cases of CVD were detected. Prevalence of CVD was 1.4 percent in black boys, 2.6 in Hispanic boys, 3.1 percent in Asian boys, and 5.6 in non-Hispanic white boys. In girls, the prevalence of CVD was less than 1 percent across all ethnic groups.

    Of the 59 CVD cases in boys, 19 (32 percent) were mild, nine (15 percent) were moderate, 24 (41 percent) were severe, and seven (12 percent) were not classifiable. Of the four CVD cases in girls, two were mild, one was severe, and the other was unclassified.


    American Journal of Ophthalmology

    Co-occurrence of Acute Retinal Artery Occlusion and Acute Ischemic Stroke

    June AJO

    Lee et al. evaluated the co-occurrence of acute ischemic stroke and acute retinal artery occlusion (RAO) in a retrospective observational case series. Acute cerebral infarction accompanied RAO in almost 1 out of 4 subjects. The underlying causes of RAO were more frequently identified in patients with concomitant acute ischemic stroke, as identified on diffusion-weighted magnetic resonance imaging (MRI), than in those without concomitant acute ischemic stroke.

    The study included 33 consecutive patients with acute RAO who underwent diffusion-weighted MRI within seven days of the onset of visual symptoms. The causes of RAO were classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria, which are based on clinical features and the results of etiological evaluations for atherosclerosis, cardioembolism, and other prothrombotic conditions. Acute ischemic stroke was detected in eight subjects (24 percent) with RAO. Among these subjects, three patients (38 percent) did not exhibit any neurologic symptoms or signs. Most of the infarction patterns were small, multiple, and scattered.

    All of the subjects with RAO who were positive for lesions on diffusion-weighted MRI had identifiable causes for the occlusion, whereas only 36 percent of the subjects who were negative for lesions had identifiable etiologies. Carotid stenosis or cardioembolic sources were found more commonly in cases of central RAO than in cases of branch RAO. 

    Effects of Intravitreal Anti-VEGF Injections on Intraocular Pressure

    June AJO

    Using a retrospective cohort study design, Kim et al. evaluated the long-term effects of multiple intravitreal anti–vascular endothelial growth factor (VEGF) injections on IOP in eyes with neovascular age-related macular degeneration (AMD) or retinal vein occlusion (RVO). 

    This study enrolled patients who underwent multiple (more than three) intravitreal anti-VEGF injections and were followed for more than 12 months after their last injection. IOP elevation was defined as an increase of 5 mmHg over the baseline measurement on two consecutive visits. The frequency of IOP elevation was determined. A hazard ratio of each putative risk factor for IOP elevation was calculated using the Cox proportional hazard model for all participants, incorporating underlying disease as a covariate, as well as for each cohort.

    Included in the analysis were 629 eyes with neovascular AMD and 95 eyes with RVO. Twenty eyes with neovascular AMD (3 percent) and seven eyes with RVO (7 percent) experienced IOP elevation after multiple anti-VEGF injections, with an overall incidence of 4 percent. In the Cox proportional hazard analysis of total participants, a diagnosis of RVO, a history of glaucoma, and low baseline IOP were all significant risk factors for IOP elevation after multiple anti-VEGF injections.

    The authors concluded that a history of multiple intravitreal anti-VEGF injections was not a significant risk factor for IOP elevation in this study. IOP elevation was more common in eyes with RVO than those with AMD after anti-VEGF injection.

    Floppy Iris and Prevalence of Intraoperative Cataract Surgery Complications

    June AJO

    Vollman et al. performed a retrospective analysis of 4,923 cataract surgery cases from the Veterans Affairs Ophthalmic Surgical Outcomes Data Project to determine the incidence of intraoperative floppy iris syndrome (IFIS) and its association with the use of alpha-antagonists as well as the use of pupillary expansion devices. They also studied the prevalence of other complications in IFIS patients.

    Factors analyzed included IFIS, intraoperative iris trauma, intraoperative iris prolapse, posterior capsular tear, anterior capsular tear, intraoperative vitreous prolapse, use of alpha-blockers, and use of pupillary expansion devices. A total of 1,254 patients (25 percent) took alpha-blockers preoperatively (selective, 587; nonselective, 627; both, 40). Of these 1,254 patients, 428 (34 percent) developed IFIS. Moreover, among all patients with IFIS, 75 percent (428/569) had taken alpha-blockers preoperatively. In 430 patients (9 percent) a pupillary expansion device was used; of these patients, 186 (43 percent) had IFIS. Eighty-six patients with IFIS had at least one intraoperative complication, and 39 had more than one intraoperative complication.

    The authors concluded that the use of either selective or nonselective alpha-antagonists significantly increased the risk of IFIS. Nonselective alpha-antagonists caused IFIS at a higher prevalence than previously reported. Further, the study demonstrated that the odds of surgical complications are significantly increased in all groups of patients with IFIS (including those using either type of alpha-antagonist as well as those not taking these medications).

    JAMA Ophthalmology 

    Cosmetic Facial Fillers and Severe Vision Loss

    May JAMA Ophthalmology 

    Although dermal injection of cosmetic fillers can lead to irreversible blindness when injected in the forehead, Carle et al. noted that this possible adverse effect is not typically mentioned to patients. Cosmetic facial fillers are not approved for injection in the forehead, but off-label use is common.

    The authors reported on three patients with vision loss, only one of whom experienced a small amount of visual recovery associated with aggressive therapy. These patients developed central retinal artery occlusion due to fillers shortly after their cosmetic procedures. According to the authors, the filler presumably enters the central retinal artery via the rich external–internal carotid anastomoses and becomes embedded in the retinal tissues, potentially leading to severe, irreversible vision loss.

    To the authors’ knowledge, these are the first published reports of blindness caused by filler injected into the forehead.

    Folate, Vitamin B6, and Vitamin B12 in Relation to Exfoliation Glaucoma

    May JAMA Ophthalmology 

    Effective strategies for primary prevention are lacking for exfoliation glaucoma (EG), which is the most common type of secondary glaucoma. To better understand possible risk and protective factors, Kang et al. examined the association between B vitamin intake and EG or suspected EG (EG/SEG) risk in a national prospective cohort study, drawing on more than 20 years of follow-up data from the Nurses’ Health Study (NHS; all participants were women and registered nurses) and the Health Professionals Follow-up Study (HPFS; all were men and health professionals) from June 1, 1980, to May 31, 2010 (NHS), and from January 1, 1986, to December 31, 2010 (HPFS). A subset of 78,980 NHS women and 41,221 HPFS men who were 40 years or older, were free of glaucoma, had completed diet questionnaires, and reported eye examinations (follow-up rate was more than 85 percent) were included in the study. Cumulatively updated intake of B vitamins (folate, vitamin B6, and vitamin B12) was ascertained by repeated administration of validated questionnaires.

    Incident cases of EG/SEG, totaling 399 (329 women and 70 men), were identified. Multivariable relative risks for EG/SEG were calculated in each cohort and then pooled for metaanalysis. Vitamin B6 and vitamin B12 intake was not shown to be associated with EG/SEG risk in pooled analyses. However, a trend of a reduced risk was observed with higher intake of folate. These results were not materially altered after adjustment for vitamin B6 and vitamin B12 intake. An association was observed for supplemental folate intake but not for dietary folate only (p = .03 and p = .64 for linear trend, respectively). Greater frequency of multivitamin use suggested a modest inverse association (current multivitamin use of six times or more per week vs. nonuse multivariable relative risk, 0.84; 95 percent CI, 0.64-1.11; p = .06 for linear trend). The authors concluded that higher total folate intake was associated with a lower risk for EG/SEG, supporting a possible causal role of homocysteine in EG/SEG.


    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

    Genetic Modulation of Central Serous Chorioretinopathy

    Human Mutation
    Published online March 24, 2014

    Although central serous chorioretinopathy (CSCR) seems to be caused largely by external environmental factors, Schubert et al. tested the hypothesis that a genetic component directs the response to external stimuli by influencing choroidal endothelial permeability. They found the first gene/locus associated with CSCR and proposed that genetically predetermined variations in cadherin 5 (CDH5) underlie a substantial proportion of CSCR cases when combined with triggering events such as corticosteroid treatment or severe hormonal imbalance.

    The researchers studied the association of genetic variation in 44 genes from stress response and corticosteroid metabolism pathways with the CSCR phenotype in two independent cohorts of 400 CSCR cases and 1,400 matched controls. They found a significant association of four common CDH5 single-nucleotide polymorphisms with CSCR in male patients in both cohorts. A common haplotype was present in 25.4 percent of the male CSCR cases and in 35.8 percent of the controls.

    If these results are confirmed, the researchers said, the data could serve as a basis for pretreatment genetic screening of male patients to identify those who are at increased risk of developing CSCR following corticosteroid treatment.

    Vitrectomy for Floaters

    November 2013

    Sebag et al. investigated whether vitrectomy is safe and effective as a treatment for floaters. They found that the procedure can normalize contrast sensitivity and alleviate self-reported visual dissatisfaction.

    For this study, the researchers reported results from two studies: an efficacy study of 16 patients (16 eyes) and a safety study of 49 patients (60 eyes). In both studies, a single surgeon performed minimally invasive sutureless three-port vitrectomy with 25-gauge instruments. The surgeon did not remove peripheral vitreous and used nonhollow probes for cannula extraction. No cases involved an intraoperatively induced posterior vitreous detachment. The NEI Visual Function Questionnaire was used to assess patient satisfaction with outcomes.

    In the efficacy study, postoperative contrast sensitivity function (CSF) normalized at one week and remained normal at the one- and three-month follow-up visits. All but one patient experienced a complete resolution of floater symptoms.

    In the safety study, no patient developed retinal breaks, retinal detachments, endophthalmitis, intraocular hemorrhage, or glaucoma. One patient had macular pucker that was successfully treated with surgical peeling; a second patient developed clinically significant floaters, which required repeat vitrectomy.

    MD Satisfaction With Laser Vision Correction

    Journal of Cataract & Refractive Surgery

    How happy are physicians who have undergone laser vision correction? Pasquali et al. assessed quality of life and satisfaction among doctors who had refractive surgery at one eye institute between 2000 and 2012. They found a high level of satisfaction in these patients.

    For this cohort study, the researchers developed a 12-question survey targeted to physicians. Questions covered issues specific to medical practice (such as ability to perform procedures accurately) as well as more general refractive concerns (such as residual need for glasses or contact lenses).

    A chart review identified 226 physicians who had undergone PRK or LASIK. Of the 128 who completed the survey (including nine ophthalmologists), 96 percent said that they would repeat the surgery, 97 percent reported that their vision was the same or better than it was before, and 39 percent reported that they could perform procedures much more easily or better than they could before surgery. Five patients, one of whom was an ophthalmologist, said that they would not have the procedure again.

    This is the first study to evaluate refractive surgery exclusively in a physician population.


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