American Journal of Ophthalmology

Why Does the Healthy Cornea Resist Pseudomonas aeruginosa Infection?

David J. Evans, Suzanne M.J. Fleiszig — 2013-04-18

Purpose: To provide our perspective on why the cornea is resistant to infection based on our research results with Pseudomonas (P) aeruginosa. We focus on our current understanding of the interplay between bacteria, tear fluid, and the corneal epithelium that determines health as the usual outcome, and propose a theoretical model for how contact lens wear might change those interactions to enable susceptibility to P aeruginosa infection.Methods: Use of “null-infection” in vivo models, cultured human corneal epithelial cells, contact lens–wearing animal models, and bacterial genetics help to elucidate mechanisms by which P aeruginosa survives at the ocular surface, adheres, and traverses multilayered corneal epithelia. These models also help elucidate the molecular mechanisms of corneal epithelial innate defense.Results: Tear fluid and the corneal epithelium combine to make a formidable defense against P aeruginosa infection of the cornea. Part of that defense involves the expression of antimicrobials such as β-defensins, the cathelicidin LL-37, cytokeratin-derived antimicrobial peptides, and RNase7. Immunomodulators such as SP-D and ST2 also contribute. Innate defenses of the cornea depend in part on MyD88, a key adaptor protein of TLR and IL-1R signaling, but the basal lamina represents the final barrier to bacterial penetration. Overcoming these defenses involves P aeruginosa adaptation, expression of the type III secretion system, proteases, and P aeruginosa biofilm formation on contact lenses.Conclusion: After more than 2 decades of research focused on understanding how contact lens wear predisposes to P aeruginosa infection, our working hypothesis places blame for microbial keratitis on bacterial adaptation to ocular surface defenses, combined with changes to the biochemistry of the corneal surface caused by trapping bacteria and tear fluid against the cornea under the lens.

The Rate of Structural Change: The Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study

2013-03-14

Purpose: To compare rates of topographic change in ocular hypertensive eyes that develop primary open-angle glaucoma (POAG) compared to eyes that do not, and to identify factors that influence the rate of change.Design: Longitudinal, randomized clinical trial.Methods: Four hundred forty-one participants (832 eyes) in the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study were included. POAG was defined as repeatable visual field, photography-based optic disc changes, or both. The rate of topographic change in the 52 participants (66 eyes) who developed POAG was compared with that of participants who did not develop POAG using multivariable mixed effects models.Results: In both univariate and multivariate analyses, the rate of rim area loss was significantly faster in eyes in which POAG developed than in eyes in which it did not (univariate mean, −0.0131 mm2/year and −0.0026 mm2/year, respectively). The significantly faster rate of rim area loss in black persons found in the univariate analysis did not remain significant when baseline disc area was included in the model. In multivariate analyses, the rate of rim area loss and other topographic parameters also was significantly faster in eyes with worse baseline visual field pattern standard deviation and higher intraocular pressure during follow-up. Moreover, a significant rate of rim area loss was detected in eyes in which POAG did not develop (P < .0001). The rate of rim area loss in eyes with an optic disc POAG endpoint was significantly faster than in those with a visual field POAG endpoint.Conclusions: The rate of rim area loss is approximately 5 times faster in eyes in which POAG developed compared with eyes in which it did not. These results suggest that measuring the rate of structural change can provide important information for the clinical management of ocular hypertensive patients. Additional follow-up is needed to determine whether the statistically significant change in the eyes in which POAG did not develop represents normal aging or glaucomatous change not detected by conventional methods.

Agreement of Flicker Chronoscopy for Structural Glaucomatous Progression Detection and Factors Associated With Progression

Ru-Ik Chee, Fabiana Q. Silva, Joshua R. Ehrlich, Nathan M. Radcliffe — 2013-02-25

Purpose: To evaluate agreement of flicker chronoscopy for structural glaucomatous progression detection and factors associated with progression.Design: Retrospective cohort study.Methods: Two glaucoma fellowship–trained ophthalmologists, masked to temporal sequence, independently graded serial flicker chronoscopy images from 1 eye of a cohort of glaucoma patients for features of structural progression. Agreement between graders was determined, as was accuracy for determining the temporal order of images. After adjudication, simple and multiple logistic models were constructed to determine baseline variables associated with increased odds of progression.Results: Fifty of 103 included eyes/patients (48.5%) had at least 1 sign of structural progression. Temporal sequence was incorrectly determined in 14 of 206 cases (6.4%). Interobserver agreements for identifying baseline photographs (κ = 0.9), global progression (κ = 0.7), parapapillary atrophy (PPA) progression (κ = 0.7), disc hemorrhages (κ = 0.7), neuroretinal rim loss (κ = 0.5), and retinal nerve fiber layer (RNFL) loss (κ = 0.2) were calculated. Age was significantly associated with global (1.8; 1.3-2.6, P < .001) (odds ratio; 95% confidence interval, significance) and PPA progression (1.7; 1.2-2.4, P = .002). Lower corneal hysteresis was associated with global progression (0.78; 0.56-0.99, P = .049) and RNFL loss (0.5; 0.3-0.9, P = .02). Goldmann-correlated intraocular pressure (1.0, 0.7-1.4, P = .9), visual field mean deviation (1.0, 0.9-1.0, P = .2), and central corneal thickness (0.9, 0.8-1.0, P = .1) were not significantly associated with progression. On multivariable analysis, only age was associated with global progression (1.8; 1.2-2.5, P = .002).Conclusion: Flicker chronoscopy demonstrated acceptable interobserver agreement in structural progression detection. Corneal hysteresis and age were both associated with progression, but age was the only significant factor on multivariable analysis.

Myopia-Related Fundus Changes in Singapore Adults With High Myopia

2013-03-15

Purpose: To examine the pattern of myopia-related macular and optic disc changes in Singapore adults with high myopia (spherical equivalent ≤−6.00 diopters).Design: Asian adults with high myopia from 3 population-based surveys.Methods: Adults 40 years and older (n = 359) with high myopia were pooled from 3 population-based surveys in Singapore Asians: (1) the Singapore Prospective Study Program (SP2, n = 184); (2) the Singapore Malay Eye Study (SiMES, n = 98); and (3) the Singapore Indian Eye Study (SINDI, n = 77). All study participants underwent standardized refraction and fundus photography, and SiMES and SINDI subjects also completed ocular biometry measurements. Myopia-related macular (posterior staphyloma, lacquer cracks, Fuchs spot, myopic chorioretinal atrophy, and myopic choroidal neovascularization) and optic disc (optic nerve head tilt, optic disc dimensions, and peripapillary atrophy) changes were evaluated.Results: The most common myopia-related macular finding in adults with high myopia was staphyloma (23%), followed by chorioretinal atrophy (19.3%). There were few cases of lacquer crack (n = 6, 1.8%), T-sign (n = 6, 1.8%), retinal hemorrhage (n = 3, 0.9%), active myopic choroidal neovascularization (n = 3, 0.9%), and no case of Fuchs spot. The most common disc finding associated with high myopia was peripapillary atrophy (81.2%), followed by disc tilt (57.4%). Staphyloma and chorioretinal atrophy increased in prevalence with increasing age, increasing myopic refractive error, and increasing axial length (all P < .001). Ethnicity comparisons demonstrated the highest proportion of staphyloma (P = .04) among Malays, the highest proportion of peripapillary atrophy (P = .01) and disc tilt (P < .001) among Chinese, and the largest cup-to-disc ratio (P < .001) among Indians.Conclusions: Staphyloma and chorioretinal atrophy lesions were the most common fundus findings among Asian adults with high myopia. In this population, tilted discs and peripapillary atrophy were also common, while choroidal neovascularization and Fuchs spot were rare. In contrast with Singapore teenagers, in whom tilted disc and peripapillary atrophy were common while staphyloma and chorioretinal atrophy were rare, pathologic myopia appears to be dependent on the duration of disease and, thus, age of the individual.

16 and 24 Gy Low-voltage X-ray Irradiation With Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration: 12-Month Outcomes

2013-03-14

Purpose: To describe the 12-month safety and efficacy outcomes of 16 or 24 Gy radiation using low-voltage x-ray irradiation in conjunction with intravitreal ranibizumab for neovascular age-related macular degeneration (AMD).Design: Prospective, phase I, open-label, nonrandomized uncontrolled safety study.Methods: setting: Institutional. study population: Neovascular AMD patients. intervention: One x-ray irradiation treatment at 16 or 24 Gy was administered externally through 3 locations in the inferior pars plana. After 2 initial monthly loading doses of ranibizumab, subsequent ranibizumab was administered according to predetermined criteria. main outcome measures: Visual acuity, number of ranibizumab injections, safety and efficacy metrics at 12 months.Results: Forty-seven eyes of 47 patients were enrolled and completed 12 months of follow-up: 16 Gy (n = 28) and 24 Gy (n = 19). There was no evidence of radiation retinopathy, optic neuropathy, or cataract. The mean visual acuity improved in both groups: +8.4 ± 11.9 letters and +7.8 ± 12 letters for 16 and 24 Gy, respectively. In both groups, 100% of subjects lost <15 letters, with 76% and 79% gaining ≥0 letters in the 16 Gy and 24 Gy groups, respectively. Patients received a mean of 1.0 additional injection over 12 months. The mean change in optical coherence tomography central subfield thickness from baseline to month 12 was −107 and −87 μm for the 16 Gy and 24 Gy groups, respectively.Conclusion: One treatment of 16 or 24 Gy low-voltage x-ray therapy with as-needed ranibizumab appears safe in subjects with neovascular AMD at 12 months. An overall improvement in visual acuity was observed. No radiation-related adverse effects were reported.

Management of Submacular Hemorrhage Secondary to Neovascular Age-Related Macular Degeneration With Anti–Vascular Endothelial Growth Factor Monotherapy

2013-02-26

Purpose: To report the visual and anatomic outcomes of anti–vascular endothelial growth factor (VEGF) monotherapy in the management of marked submacular hemorrhage secondary to neovascular age-related macular degeneration (AMD).Design: Retrospective, interventional, consecutive case series.Methods: Nineteen eyes of 18 patients with neovascular AMD and fovea involving submacular hemorrhage comprising greater than 50% of the lesion area were treated with anti-VEGF monotherapy. Main outcome measures included mean visual acuity change from baseline, mean central lesion thickness change from baseline, mean number of injections at 6 months, and adverse events. Snellen visual acuity was converted to approximate ETDRS letter score for the purpose of statistical analysis.Results: The mean change in approximate ETDRS letter score from baseline was +12 letters at 3 months (P = .003), +18 letters at 6 months (P = .001), and +17 letters at 12 months follow-up (P = .02). Seven eyes received ranibizumab, 6 eyes received bevacizumab, and 6 eyes received both at various time points. The mean number of injections at 6 months was 4.7. The mean OCT central lesion thickness decreased from 755 μm to 349 μm at 6 months follow-up (P = .0008).Conclusions: Management with anti-VEGF monotherapy may yield visual and anatomic improvements in eyes with marked submacular hemorrhage secondary to neovascular AMD.

Displacement of the Retina and Its Recovery After Vitrectomy in Idiopathic Epiretinal Membrane

2013-03-15

Objective: To study the displacement of the retina and its change after vitrectomy in idiopathic epiretinal membrane (ERM).Design: Prospective, interventional case series.Methods: Fifty-six eyes of 53 consecutive patients with ERM underwent vitrectomy with ERM removal and internal limiting membrane peeling. Fundus autofluorescence (FAF) imaging was examined before and at 1, 3, 6, and 12 months after vitrectomy. Main outcome measures were the proportion of eyes with retinal displacement for ERM detected by FAF imaging and the recovery rate of retinal displacement after vitrectomy.Results: Before surgery, FAF photography demonstrated hyperautofluorescent lines within the vascular arcade in 37 (66.1%) of the 56 eyes. The lines seemed to be consistent with the location of the retinal vessels before their displacement. These hyperautofluorescent lines appeared significantly more frequently among patients in whom the disease duration was 3 years or less. In 23 (62.2%) of these 37 eyes, within the first postoperative month, the hyperautofluorescent lines disappeared. The disappearance of the hyperautofluorescent line was thought to be the result of the return of the retinal vessel to its original position. Greater visual improvements (logarithm of the minimal angle of resolution, ≥0.3) were statistically significantly obtained in patients in whom the hyperautofluorescent lines had become indistinct at 1 month after surgery (P < .05).Conclusions: Hyperautofluorescent lines indicating retinal displacement were found by FAF in 66.1% of patients before surgery for ERM. In addition, retinal displacement was significantly more common among patients who had experienced subjective symptoms for 3 years or less. Fundus autofluorescence is useful for predicting postoperative visual acuity improvement.

Risk Factors for Development of Full-Thickness Macular Holes After Pars Plana Vitrectomy for Myopic Foveoschisis

Xinxiao Gao, Yasushi Ikuno, Satoko Fujimoto, Kohji Nishida — 2013-03-20

Purpose: To identify risk factors for development of secondary full-thickness macular holes after pars plana vitrectomy with internal limiting membrane (ILM) peeling for myopic foveoschisis.Design: Retrospective, interventional case series.Methods: We retrospectively reviewed the records of 42 eyes (42 patients) treated with pars plana vitrectomy (vitreous separation, internal limiting membrane peeling, and gas tamponade) for myopic foveoschisis with and without a retinal detachment but without a macular hole from January 2002 through June 2012. Cataract surgery was performed in all phakic eyes. Patients were followed up for 6 months after the initial surgery, and optical coherence tomography images were obtained at every visit. The factors associated with development of postoperative full-thickness macular holes were investigated.Results: A postoperative macular hole developed in 8 (19.0%) eyes. No significant correlations of age (P = .369), axial length (P = .113), visual acuity (P = .859), foveal status (P = .331), posterior staphyloma (P = 1.000), or chorioretinal atrophy (P = .837) were found between patients with and without secondary macular holes. Among the characteristics seen on the optical coherence tomography images, the percentage of eyes with an inner segment/outer segment junction defect was significantly (P = .013, Fisher exact test) higher in patients with a macular hole than in those without a macular hole. Logistic regression analysis showed that only an inner segment/outer segment junction defect (P = .018) was a significant risk factor for development of secondary macular holes.Conclusions: Secondary macular holes can develop in myopic foveoschisis after pars plana vitrectomy with internal limiting membrane peeling. A preoperative inner segment/outer segment junction defect can be a risk factor for development of a macular hole.

Intraocular Concentrations of Cytokines and Chemokines in Rhegmatogenous Retinal Detachment and the Effect of Intravitreal Triamcinolone Acetonide

2013-03-13

Purpose: To investigate the role of intravitreal injection of triamcinolone acetonide (IVTA) in preventing photoreceptor apoptosis in eyes with rhegmatogenous retinal detachment (RRD) by measuring cytokine levels in the aqueous humor before and after IVTA.Design: Prospective, nonrandomized, interventional case series.Methods: setting: Institutional. patients: Nineteen eyes of 19 consecutive patients with RRD. intervention: All 19 eyes underwent IVTA 1 day before 25-gauge vitrectomy. Seventeen eyes free of retinal vascular disease served as controls. main outcome measure: Both baseline and 1 day post-IVTA measurements were made of the relative concentrations of 15 soluble factors (3 cytokines, 7 chemokines, and 5 growth factors). The associations with clinical findings, including macular status, were then analyzed.Results: Elevated monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1β (MIP-1β), and interferon γ–induced protein 10 (IP-10) in eyes with RRD were significantly reduced after IVTA. MCP-1 levels were significantly correlated with MIP-1β and IP-10 before and after IVTA. The decreases in MCP-1, MIP-1β, and IP-10 were also closely correlated to each other. Both before and after IVTA, MCP-1 was higher in eyes with macula-off RRD than in eyes with macula-on RRD.Conclusions: IVTA suppressed elevated levels of intraocular MCP-1, MIP-1β, and IP-10 in eyes with RRD. The decrease in the aqueous levels of each of these factors was significantly correlated with the others. In addition to MCP-1, MIP-1β and IP-10 might potentially be additional target molecules for RRD therapy.

Characterization of Ischemic Index Using Ultra-widefield Fluorescein Angiography in Patients With Focal and Diffuse Recalcitrant Diabetic Macular Edema

2013-02-28

Purpose: To explore the association of angiographic nonperfusion in focal and diffuse recalcitrant diabetic macular edema (DME) in diabetic retinopathy (DR).Design: A retrospective, observational case series of patients with the diagnosis of recalcitrant DME for at least 2 years placed into 1 of 4 cohorts based on the degree of DR.Methods: A total of 148 eyes of 76 patients met the inclusion criteria at 1 academic institution. Ultra-widefield fluorescein angiography (FA) images and spectral-domain optical coherence tomography (SD OCT) images were obtained on all patients. Ultra-widefield FA images were graded for quantity of nonperfusion, which was used to calculate ischemic index. Main outcome measures were mean ischemic index, mean change in central macular thickness (CMT), and mean number of macular photocoagulation treatments over the 2-year study period.Results: The mean ischemic index was 47% (SD 25%; range 0%-99%). The mean ischemic index of eyes within Cohorts 1, 2, 3, and 4 was 0%, 34% (range 16%-51%), 53% (range 32%-89%), and 65% (range 47%-99%), respectively. The mean percentage decrease in CMT in Cohorts 1, 2, 3, and 4 were 25.2%, 19.1%, 11.6%, and 7.2%, respectively. The mean number of macular photocoagulation treatments in Cohorts 1, 2, 3, and 4 was 2.3, 4.8, 5.3, and 5.7, respectively.Conclusions: Eyes with larger areas of retinal nonperfusion and greater severity of DR were found to have the most recalcitrant DME, as evidenced by a greater number of macular photocoagulation treatments and less reduction in SD OCT CMT compared with eyes without retinal nonperfusion. Areas of untreated retinal nonperfusion may generate biochemical mediators that promote ischemia and recalcitrant DME.

Comparison of Cone Pathologic Changes in Idiopathic Macular Telangiectasia Types 1 and 2 Using Adaptive Optics Scanning Laser Ophthalmoscopy

2013-02-26

Purpose: To compare pathologic changes in the photoreceptors of eyes with idiopathic macular telangiectasia types 1 and 2 using adaptive optics scanning laser ophthalmoscopy (AO-SLO).Design: Prospective cross-sectional study.Methods: Eleven eyes with idiopathic macular telangiectasia type 1, 14 eyes with type 2, and 10 normal eyes underwent a full ophthalmologic examination, spectral-domain optical coherence tomography (SD-OCT), and imaging with an original prototype AO-SLO system. All eyes with idiopathic macular telangiectasia were examined with fluorescein angiography (FA), confocal blue reflectance, and microperimetry.Results: Compared with normal eyes (29 017 ± 5507 cones/mm2), those with idiopathic macular telangiectasia type 1 had significantly lower cone density on the temporal side (18 427 ± 4908 cones/mm2, P = .010). The FA leakage area (5.90 ± 3.23 mm2) was larger than the dark regions (2.45 ± 2.40 mm2) on AO-SLO (P = .003)—which were observed only in the FA leakage area. Compared with normal eyes, those with idiopathic macular telangiectasia type 2 had significantly lower cone density in all areas (P < .05 for all). Patchy dark regions were also seen in areas without FA abnormalities in 12 eyes. Higher mean retinal sensitivity correlated with greater mean cone density 0.5 mm from the center of the fovea (type 1: P = .010; type 2: P < .001).Conclusions: Idiopathic macular telangiectasia type-specific differences in the distribution of photoreceptor abnormalities were shown in the AO-SLO images. For both idiopathic macular telangiectasia types 1 and 2, visual impairment was associated with cone damage.

Imaging Retinal Pigment Epithelial Proliferation Secondary to PASCAL Photocoagulation In Vivo by Polarization-sensitive Optical Coherence Tomography

2013-02-25

Purpose: To image the retinal pigment epithelium (RPE) after macular laser and to monitor healing responses over time in vivo in patients with diabetic maculopathy using polarization-sensitive optical coherence tomography (OCT).Design: Prospective, nonrandomized clinical trial.Methods: In this single-center trial (Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria), 13 patients (13 eyes) underwent grid photocoagulation for diabetic maculopathy. Retinal healing processes were continuously followed over the course of 3 months. A polarization-sensitive OCT prototype was used, allowing detection and measurement of the RPE changes based on their specific polarization-scrambling qualities.Results: After 1 day, the intraretinal photocoagulation lesions were sharply demarcated, whereas RPE changes were rather subtle. At 1 week, all lesions exhibited traction of the inner retinal layers toward the RPE and loss of photoreceptor cells. In tissue-sensitive polarization-sensitive OCT imaging, polarization-scrambling columns were found at the level of the RPE. During follow-up, different healing responses were seen in the polarization-scrambling RPE layer, ranging from hyperproliferation to focal atrophy.Conclusion: Because of the properties of the polarization state of backscattered light, polarization-sensitive OCT revealed specific morphologic changes in the RPE and outer retinal layers secondary to retinal laser treatment undetectable with intensity-based spectral-domain OCT. The increase in polarization-scrambling tissue over the course of 3 months indicates a more intense healing reaction and proliferation of RPE cells than previously characterized in rodent studies.

Association of Complement Factor H Tyrosine 402 Histidine Genotype with Posterior Involvement in Sarcoid-Related Uveitis

2013-03-14

Purpose: To determine whether the complement factor H (CFH) tyrosine 402 histidine (Y402H) variant, recently shown to be associated with age-related macular degeneration (AMD) and multifocal choroiditis, is associated with specific ocular sarcoidosis clinical phenotypes in black and white persons.Design: Case-control study.Methods: The CFH Y402H polymorphism (rs1061170) was genotyped in 41 subjects with ocular sarcoidosis and 393 control subjects. Allele frequencies in the ocular sarcoidosis cases were compared with controls using chi-square score tests. Genotypic model-based (dominant, recessive, and additive) associations of the rs1061170 allele were tested using multivariate logistic regression. Bayesian information criteria were used to formalize model selection. Genotypes were correlated with disease characteristics and severity of ocular inflammation.Results: The C allele (rs1061170) was found in 35% of controls, but occurred with a significantly higher frequency (48.7%) in ocular sarcoidosis cases (odds ratio, 1.72; 95% confidence interval, 1.09 to 2.78; P = .018). Logistic regression demonstrated an association between rs1061170 and ocular sarcoidosis in 2 of 3 genetic models (additive, P = .0078; recessive, P = .0018). Posterior uveitis and panuveitis were overrepresented significantly in cases with the homozygous variant genotype (CC, 91%; P = .047). The population-attributable risk related to this CFH risk variant was 20%.Conclusions: The Y402H polymorphism of CFH seems to be associated with ocular sarcoidosis in black and white persons. Carriage of the CFH Y402H polymorphism in both alleles is associated with an increased risk for posterior uveitis and panuveitis presentation. The prognostic importance of this genotype will require prolonged follow-up studies.

A Longitudinal Study of Stargardt Disease: Clinical and Electrophysiologic Assessment, Progression, and Genotype Correlations

2013-03-15

Purpose: To investigate the clinical and electrophysiologic natural history of Stargardt disease and correlate with the genotype.Design: Cohort study of 59 patients.Methods: Clinical history, examination, and electrophysiologic assessment were undertaken in a longitudinal survey. Patients were classified into 3 groups based on electrophysiologic findings, as previously published: Group 1 had dysfunction confined to the macula; Group 2 had macular and generalized cone system dysfunction; and Group 3 had macular and both generalized cone and rod system dysfunction. At baseline, there were 27 patients in Group 1, 17 in Group 2, and 15 in Group 3. Amplitude reduction of >50% in the relevant electroretinogram (ERG) component or a peak time shift of >3 ms for the 30 Hz flicker ERG or bright flash a-wave was considered clinically significant ERG deterioration. Molecular screening of ABCA4 was undertaken.Results: The mean age at baseline was 31.7 years, with the mean follow-up interval being 10.5 years. A total of 22% of patients from Group 1 showed ERG group transition during follow-up, with 11% progressing to Group 2 and 11% to Group 3. Forty-seven percent of patients in Group 2 progressed to Group 3. There was clinically significant ERG deterioration in 54% of all subjects: 22% of Group 1, 65% of Group 2, and 100% of Group 3. At least 1 disease-causing ABCA4 variant was identified in 47 patients.Conclusions: All patients with initial rod ERG involvement demonstrated clinically significant electrophysiologic deterioration; only 20% of patients with normal full-field ERGs at baseline showed clinically significant progression. Such data assist counseling by providing more accurate prognostic information and are also highly relevant in the design, patient selection, and monitoring of potential therapeutic interventions.

Visual Outcomes in Children With Neurofibromatosis Type 1 and Orbitotemporal Plexiform Neurofibromas

2013-02-27

Purpose: To describe the visual outcomes and volumetric magnetic resonance imaging (3D MRI) in children with neurofibromatosis type 1 (NF1) and orbitotemporal plexiform neurofibromas.Design: Multicenter retrospective case series.Methods: Two institutions with dedicated NF1 clinical research programs queried their established clinical databases for children with orbitotemporal plexiform neurofibromas. Visual acuity, refractive error, ambylopia, and treatment history were abstracted. Extent of orbitotemporal plexiform neurofibroma involvement was assessed clinically and with 3D MRI analysis. Children with optic pathway gliomas or ocular causes of decreased visual acuity (ie, cataracts, glaucoma) other than strabismus or anisometropia were excluded.Results: Twenty-one children met inclusion criteria (median age 8 years, range 0.33-23 years). Orbitotemporal plexiform neurofibroma location was classified as isolated eyelid (n = 6), eyelid and orbit (n = 7), orbit and temporal region (n = 7), or diffuse orbit (n = 1). Three subjects had bilateral orbital involvement. Amblyopia secondary to the orbitotemporal plexiform neurofibroma was present in 13 subjects (62%) and was caused by strabismus (n = 2, 10%), occlusion from ptosis (n = 9, 43%), or anisometropia (n = 9, 43%), or a combination of factors (n = 6, 29%). MRI-derived volumes were measured in 19 subjects (median 41.8 mL, range 2.7-754 mL). All subjects with amblyopia had orbitotemporal plexiform neurofibroma volumes greater than 10 mL.Conclusion: In our series, amblyopia occurs in more than half of NF1 children with orbitotemporal plexiform neurofibromas, most commonly because of ptosis and anisometropia. The 3D MRI analysis allowed for sensitive measurement of orbitotemporal plexiform neurofibroma size, and larger volumes were associated with development of amblyopia.

Topical Linezolid 0.2% for the Treatment of Vancomycin-Resistant or Vancomycin-Intolerant Gram-Positive Bacterial Keratitis

Elmer Yuchen Tu, Sandeep Jain — 2013-02-27

Purpose: To report the successful use of topical linezolid 0.2% in the treatment of gram-positive bacterial keratitis.Study Design: Retrospective, interventional case series.Methods: All cases of bacterial keratitis treated at the University of Illinois Eye and Ear Infirmary with topical linezolid were identified from the Cornea and External Disease Clinic and were reviewed for culture results, prior therapy, clinical course, and visual outcome.Results: Three patients received topical linezolid, all for cases of culture-positive or presumed gram-positive keratitis. Cases consisted of 1 patient with recalcitrant vancomycin-resistant Enterococcus faecalis (VRE) and 2 patients with infectious crystalline keratitis, 1 previously culture-positive for an uncharacterized Staphylococcus and the other for Streptococcus mitis. All 3 patients had rapid resolution of their infectious keratitis and noted no pain or discomfort attributed to the topical therapy. The patient with VRE keratitis developed a consecutive Candida keratitis elsewhere in the same cornea at the end of therapy for her VRE keratitis.Conclusion: Topical linezolid 0.2% can be an effective ophthalmic antibiotic for the treatment of gram-positive keratitis, including VRE, and is both significantly more comfortable and less immediately toxic to the ocular surface than topical vancomycin.

Meibomian Gland Morphology in Japanese Infants, Children, and Adults Observed Using a Mobile Pen-shaped Infrared Meibography Device

Rika Shirakawa, Reiko Arita, Shiro Amano — 2013-03-14

Purpose: To compare meibomian gland morphology between children and adults.Design: Cross-sectional, observational case series.Methods: In an institutional setting, healthy pediatric (n = 78, 30 boys, 48 girls; mean age ± standard deviation, 4.1 ± 3.4 years; range 1 month - 12 years) and adult (n = 25, 11 men, 14 women; 31.3 ± 4.8 years; range 24-39 years) volunteers participated in the study. A noninvasive mobile pen-shaped infrared meibography device was used to observe the meibomian glands. Lost meibomian gland area (meiboscore) was scored from grade 0 (no meibomian gland loss) through grade 3 (>two-thirds of the total area lost). The number of meibomian glands in each eyelid was counted by reviewing the video. Eyelid width was measured using a ruler. Meibomian gland density was calculated as the number of meibomian glands divided by the eyelid width.Results: The numbers of meibomian glands in the upper/lower eyelids were 26.9 ± 3.9 / 22.0 ± 2.2 in the pediatric group and 28.1 ± 2.7 / 24.4 ± 2.6 in the adult group (P = .22, P < .0001). Eyelid width was 24.4 ± 2.4 mm in the pediatric group and 27.9 ± 1.57 mm in the adult group (P < .0001). Meibomian gland densities in the upper/lower eyelids were 1.09 ± 0.17 / 0.91 ± 0.11 in the pediatric group and 1.01 ± 0.12 / 0.88 ± 0.10 in the adult group (P = .03, P = .45).Conclusions: The mobile pen-shaped infrared meibography device is useful for obtaining information on the meibomian gland structure, not only in adults but also in children, including infants. The morphology of the meibomian glands in children was the same as that in adults, distributing across the whole tarsal plates in both the upper and lower eyelids.

Correlation Between Quantitative Measurements of Tear Film Lipid Layer Thickness and Meibomian Gland Loss in Patients With Obstructive Meibomian Gland Dysfunction and Normal Controls

Youngsub Eom, Jong-Suk Lee, Su-Yeon Kang, Hyo Myung Kim, Jong-Suk Song — 2013-02-26

Purpose: To evaluate the correlation between tear film lipid layer thickness and other objective measurements such as tear film break-up time (TBUT), upper and lower meibomian gland losses, and Schirmer 1 test in patients with obstructive meibomian gland dysfunction (MGD) and normal controls.Design: Cross-sectional study.Methods: Thirty eyes of 30 patients with obstructive MGD and 25 eyes of 25 normal controls were enrolled. Lipid layer thickness was measured using an interferometer. Tear film stability and tear production were evaluated by TBUT and Schirmer 1 test. Upper and lower meibomian gland losses were evaluated using noncontact meibography. The correlations among variables were evaluated in the obstructive MGD group and the control group.Results: TBUT was significantly shorter in the obstructive MGD group than in the control group (P < .001). Upper and lower meibomian gland losses were higher in the obstructive MGD group than in the control group (P < .001 and P < .001, respectively), and lipid layer thickness was significantly thicker in the control group than in the obstructive MGD group (P = .028). Lipid layer thickness was significantly negatively correlated with upper and lower meibomian gland losses in both groups.Conclusions: Lipid layer thickness objectively measured with the interferometer was significantly thicker in the control group than in the obstructive MGD group. Lipid layer thickness was negatively correlated with upper and lower meibomian gland losses in the control group as well as in the obstructive MGD group.

Excimer Laser Phototherapeutic Keratectomy in Eyes With Corneal Stromal Dystrophies With and Without a Corneal Graft

2013-02-25

Purpose: To evaluate and compare the visual outcomes and recurrence patterns of corneal stromal dystrophies after excimer laser phototherapeutic keratectomy (PTK) in eyes with and without a corneal graft.Design: Retrospective, comparative case series.Methods: setting: Cornea Service, Wills Eye Institute, Philadelphia Pennsylvania. study population: The patients were divided into 2 groups. Group 1 comprised patients with no graft who underwent PTK (22 eyes of 15 patients), and group 2 comprised patients who underwent PTK over a previous full-thickness graft (18 eyes of 14 patients). intervention: All patients underwent PTK for decreased vision, symptoms of recurrent erosions, or both. main outcome measures: Visual outcomes and recurrence patterns of corneal stromal dystrophies.Results: Preoperative and postoperative best-corrected visual acuities were 0.46 ± 0.25 and 0.51 ± 0.27 (P = .56), respectively, in group 1 and 0.16 ± 0.13 and 0.21 ± 0.18 (P = .25), respectively, in group 2. Mean preoperative spherical equivalent was 1.54 ± 2.59 diopters (D) and −5.10 ± 5.81 D (P = .01) in groups 1 and 2, respectively, and mean postoperative spherical equivalent was 0.44 ± 1.8 D and −1.8 ± 4.25 D (P = .19) in groups 1 and 2, respectively. There was no statistically significant difference in the efficacy (P = .73) and safety (P = .62) indices between the 2 groups. In group 1, mild recurrence was seen in 7 eyes (32%) and significant recurrence was seen in 4 eyes (18%) at a mean of 32 and 47 months after PTK, respectively. In group 2, mild recurrence was seen in 5 eyes (28%) and significant recurrence was seen in 5 eyes (28%) at a mean of 36 and 50 months after PTK, respectively.Conclusions: PTK improved central corneal clarity, alleviated symptoms resulting from recurrent erosions, and improved visual acuity in both groups.

Intravitreal Bevacizumab for Retinopathy of Prematurity: Refractive Error Results

2013-03-13

Purpose: To evaluate refractive error in infants who underwent intravitreal bevacizumab injection for treatment of threshold retinopathy of prematurity (ROP).Design: Retrospective nonrandomized interventional comparative study.Methods: The study group included all infants who consecutively received a single intravitreal bevacizumab (0.375 mg or 0.625 mg) injection for therapy of threshold ROP in fundus zone I or zone II. The control group included infants who had previously undergone retinal argon laser therapy of ROP. The follow-up examination included refractometry under cycloplegic conditions.Results: The study group included 12 children (23 eyes; mean birth weight: 622 ± 153 g; gestational age: 25.2 ± 1.6 weeks) and the control group included 13 children (26 eyes; birth weight: 717 ± 197 g; gestational age: 25.3 ± 1.8 weeks). Both groups did not differ significantly in birth age and weight and follow-up. At the end of follow-up at 11.4 ± 2.3 months after birth, refractive error was less myopic in the study group than in the control group (−1.04 ± 4.24 diopters [median: 0 diopters] vs −4.41 ± 5.50 diopters [median: −5.50 diopters]; P = .02). Prevalence of moderate myopia (17% ± 8% vs 54% ± 10%; P = .02; OR: 0.18 [95% CI: 0.05, 0.68]) and high myopia (9% ± 6% vs 42% ± 10%; P = .01; OR: 0.13 [95% CI: 0.03, 0.67]) was significantly lower in the bevacizumab group. Refractive astigmatism was significantly lower in the study group (−1.0 ± 1.04 diopters vs 1.82 ± 1.41 diopters; P = .03). In multivariate analysis, myopic refractive error and astigmatism were significantly associated with laser therapy vs bevacizumab therapy (P = .04 and P = .02, respectively).Conclusions: In a 1-year follow-up, a single intravitreal bevacizumab injection as compared to conventional retinal laser coagulation was helpful for therapy of ROP and led to less myopization and less astigmatism.

Amblyopia in Childhood Eyelid Ptosis

Gregory J. Griepentrog, Nancy Diehl, Brian G. Mohney — 2013-02-19

Purpose: To report the prevalence and causes of amblyopia among children with ptosis diagnosed in a well-defined population over a 40-year period.Design: Retrospective, population-based cohort study.Methods: We retrospectively reviewed the charts of 107 patients younger than 19 years for the prevalence and causes of amblyopia who were diagnosed with childhood ptosis and were residents of Olmsted County, Minnesota, from January 1, 1965, through December 31, 2004.Results: Amblyopia was diagnosed in 16 (14.9%) of the 107 patients with childhood ptosis. Fourteen (14.6%) of 96 patients diagnosed with a congenital form of ptosis demonstrated amblyopia. Twelve (14.8%) of the 81 patients diagnosed with simple congenital ptosis had amblyopia, 7 (8.6%) cases of which solely were the result of eyelid occlusion of the visual axis. The causes of amblyopia in the remaining 5 patients were significant refractive error in 3 patients and strabismus in 2 patients.Conclusions: Amblyopia occurred in 1 in 7 children diagnosed with ptosis in this population-based cohort. In approximately half of those with amblyopia, or less than 10% of all patients, the disease solely was the result of eyelid occlusion of the visual axis.

Racial Variations in the Prevalence of Refractive Errors in the United States: The Multi-Ethnic Study of Atherosclerosis

2013-02-28

Purpose: To describe racial variations in the prevalence of refractive errors among adult white, Chinese, Hispanic, and black subjects in the United States.Design: Cross-sectional data from a prospective cohort study—the Multi-Ethnic Study of Atherosclerosis (MESA).Methods: A total of 6000 adults aged 45 to 84 years living in the United States participated in the study. Refractive error was assessed, without cycloplegia, in both eyes of all participants using an autorefractor. After excluding eyes with cataract, cataract surgery, or previous refractive surgery, the eye with the larger absolute spherical equivalent (SE) value for each participant was used to classify refractive error. Any myopia was defined as SE of -1.0 diopters (D) or less; high myopia was defined as SE of -5.0 D or less; any hyperopia was defined as SE of +1.0 D or more; clinically significant hyperopia was defined as SE of +3.0 D or more. Astigmatism was defined as a cylinder value of +1.0 D or more.Results: After excluding 508 participants with cataracts in both eyes, 838 participants with cataract surgery, 90 participants with laser refractive surgery, and 134 participants who refused to remove their contact lenses for the refraction measurement, 4430 adults with refractive error assessment in at least 1 eye contributed to the analysis. The prevalence of myopia among MESA participants was 25.1%, with lowest rates in Hispanic participants (14.2%), followed by black (21.5%) and white participants (31.0%), and highest rates in Chinese participants (37.2%). The overall rates of high myopia and astigmatism were 4.6% and 45.0%, respectively, with Chinese subjects also having the highest rates of high myopia (11.8%) and astigmatism (53.4%). The overall prevalence of any hyperopia was 38.2% and clinically significant hyperopia was 6.1%, with Hispanic participants having the highest rates of hyperopia (50.2%) and clinically significant hyperopia (8.8%). In multivariate analyses adjusting for age, sex, race, and study site, higher education level, being employed, and being taller were associated with a higher prevalence of myopia. In contrast, lower educational level and being shorter were associated with a higher prevalence of hyperopia.Conclusions: Myopia and astigmatism were most prevalent in the Chinese population, with Chinese subjects having 3 times the prevalence of myopia as Hispanic subjects. Hyperopia was most common in Hispanic subjects. These findings provide further insights into variations in refractive errors among different racial groups and have important implications for the eye care services in the United States.

Morphologic Characteristics of Optic Nerve Head Drusen on Spectral-Domain Optical Coherence Tomography

Kyoung Min Lee, Se Joon Woo, Jeong-Min Hwang — 2013-03-20

Purpose: To evaluate the morphologic characteristics of optic nerve head drusen.Design: Retrospective case series.Methods: setting: Institutional (Seoul National University Bundang Hospital). patients: Sixty-one patients with optic nerve head drusen. observation procedure: Visible and buried optic nerve head drusen were identified using funduscopy, whereas homogenous and nonhomogenous optic nerve head drusen were identified using spectral-domain optical coherence tomography images. Buried optic nerve head drusen were classified according to the size. main outcome measures: Classification of optic nerve head drusen.Results: Of 99 eyes in 61 patients, optic nerve head drusen were buried in 95 eyes and visible in 4 eyes. The patients with visible optic nerve head drusen were older on average than those with buried optic nerve head drusen (53.3 ± 8.6 years vs 13.5 ± 7.1 years; P < .001) and exhibited larger disc diameters (1643 ± 265 μm vs 1287 ± 185 μm; P = .016). All 4 eyes with visible optic nerve head drusen exhibited hyperreflective borders, which were not found in patients with buried optic nerve head drusen. Of 95 eyes with buried optic nerve head drusen, 64 eyes (67%) showed homogenous internal reflectivity, whereas 31 eyes (33%) showed nonhomogenous reflectivity with lobulations. Large optic nerve head drusen were associated with a small optic disc diameter, nonhomogenous internal reflectivity, a partial highly reflective border, intraretinal cysts, and increased temporal retinal nerve fiber layer thickness.Conclusions: Optic nerve head drusen have a diverse spectrum of spectral-domain optical coherence tomography findings associated with patient age and disc size.

Visual Field Staging Systems in Glaucoma and the Activities of Daily Living

Christoph Hirneiss — 2013-06-01

Kulkarni and associates present an important study by correlating different scoring systems of visual field defects in glaucoma patients with their vision-related functional impairment. Not only did they implement the most commonly used questionnaire instrument in ophthalmology, the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), functional impairment also was assessed by performance-based measurements (the Assessment of Disability Related to Vision Test [ADREV]). This is a very important and relatively new approach to obtain an idea of the real-life functional impairment of the glaucoma patient. The authors report that the simple visual field scoring with the mean defect (MD) performs very well with the functional impairment in terms of NEI VFQ-25 and ADREV scores. With the data presented in Tables 2 and 3, MD is correlated moderately with the NEI VFQ-25 composite score (r = 0.42 and r = 0.39 for better and worse eye, respectively) and the ADREV score (r = 0.47 and r = 0.40 for better and worse eye, respectively). Looking at these data, it is hard to understand the authors statement, that “correlations with the worse eye were far weaker” than for the better eye. With regard to the MD data above, this equals a difference in the correlation coefficient of 0.03 for the NEI VFQ-25 and 0.07 for the ADREV.

Reply

2013-06-01

We thank DR Hirneiss for his interest in our study. We agree that the absolute value of the difference in correlation coefficients was small when comparing visual field (VF) scores with the total Assessment of Disability Related to Vision score and the 25-item National Eye Institute Visual Function Questionnaire score in the better and worse eye. However, we find it noteworthy that after adjusting for age, race, and visual acuity, the VF score in the better eye was correlated more highly with visual functioning across all VF staging systems, Assessment of Disability Related to Vision subtest scores, and 25-item National Eye Institute Visual Function Questionnaire scores. The findings of Gothwal and associates corroborate ours with regard to the ability of mean defect (MD) in the better eye to predict functional ability.

Atlas of Clinical and Surgical Orbital Anatomy, Second Edition

Raymond S. Douglas, Allison N. McCoy — 2013-06-01

Media Type: Textbook, with searchable full text online Synopsis: Orbital anatomy has long been the bane of existence for eye surgeons, because of the difficulty in visualizing and conceptualizing its three dimensions. Yet a thorough understanding for orbital anatomy is critical for anyone who treats orbital disease. Atlas of Clinical and Surgical Orbital Anatomy succeeds in making this difficult subject approachable and memorable. The textbook is so practical, it might as well have been titled “Orbital Anatomy Made Ridiculously Simple” or “Orbital Anatomy For Dummies.” This second edition includes new clinical correlations and research findings, and is as useful for the fully trained oculoplastic surgeon as for the novice.

Color Atlas and Synopsis of Clinical Ophthalmology; Wills Eye Institute; Pediatric Ophthalmology

Mohamed Hussein — 2013-06-01

Media Type: Book series Synopsis: The overwhelming sea of new knowledge added to the field of pediatric ophthalmology, constantly, makes it difficult for clinicians to grasp every single detail in the field. This is particularly true for clinicians in an office setting who may often need to urgently fetch information about a particular disorder. This is when review and summary books come in handy to rescue clinicians needing this kind of help. The book titled “Color Atlas And Synopsis of Clinical Ophthalmology, Wills Eye Institute, pediatric ophthalmology” is an example of such review books, providing concise and rather comprehensive information in the field of pediatric ophthalmology.

Retinoblastoma

Zélia M. Correa — 2013-06-01

Media Type: Textbook Synopsis: The diagnosis and treatment of children with retinoblastoma have been incredibly successful since the past half century in improving survival and cure, eye preservation and, occasionally, functional vision in the affected eye (s). This book depicts a broad, comprehensive overview including differential diagnosis, natal/genetic testing and counseling, treatment, research, and future trends and research. It is essentially past, present and potential future of retinoblastoma. The editors enlisted 70 international specialists assumingly to ensure an unbiased book but weren’t completely successful. Nevertheless, this is the most comprehensive, updated review of retinoblastoma available that will fill a void in the oncology literature.

2013-06-01

American Journal of Ophthalmology

Why Does the Healthy Cornea Resist Pseudomonas aeruginosa Infection?

The Rate of Structural Change: The Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study

Agreement of Flicker Chronoscopy for Structural Glaucomatous Progression Detection and Factors Associated With Progression

Myopia-Related Fundus Changes in Singapore Adults With High Myopia

16 and 24 Gy Low-voltage X-ray Irradiation With Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration: 12-Month Outcomes

Management of Submacular Hemorrhage Secondary to Neovascular Age-Related Macular Degeneration With Anti–Vascular Endothelial Growth Factor Monotherapy

Displacement of the Retina and Its Recovery After Vitrectomy in Idiopathic Epiretinal Membrane

Risk Factors for Development of Full-Thickness Macular Holes After Pars Plana Vitrectomy for Myopic Foveoschisis

Intraocular Concentrations of Cytokines and Chemokines in Rhegmatogenous Retinal Detachment and the Effect of Intravitreal Triamcinolone Acetonide

Characterization of Ischemic Index Using Ultra-widefield Fluorescein Angiography in Patients With Focal and Diffuse Recalcitrant Diabetic Macular Edema

Comparison of Cone Pathologic Changes in Idiopathic Macular Telangiectasia Types 1 and 2 Using Adaptive Optics Scanning Laser Ophthalmoscopy

Imaging Retinal Pigment Epithelial Proliferation Secondary to PASCAL Photocoagulation In Vivo by Polarization-sensitive Optical Coherence Tomography

Association of Complement Factor H Tyrosine 402 Histidine Genotype with Posterior Involvement in Sarcoid-Related Uveitis

A Longitudinal Study of Stargardt Disease: Clinical and Electrophysiologic Assessment, Progression, and Genotype Correlations

Visual Outcomes in Children With Neurofibromatosis Type 1 and Orbitotemporal Plexiform Neurofibromas

Topical Linezolid 0.2% for the Treatment of Vancomycin-Resistant or Vancomycin-Intolerant Gram-Positive Bacterial Keratitis

Meibomian Gland Morphology in Japanese Infants, Children, and Adults Observed Using a Mobile Pen-shaped Infrared Meibography Device

Correlation Between Quantitative Measurements of Tear Film Lipid Layer Thickness and Meibomian Gland Loss in Patients With Obstructive Meibomian Gland Dysfunction and Normal Controls

Excimer Laser Phototherapeutic Keratectomy in Eyes With Corneal Stromal Dystrophies With and Without a Corneal Graft

Intravitreal Bevacizumab for Retinopathy of Prematurity: Refractive Error Results

Amblyopia in Childhood Eyelid Ptosis

Racial Variations in the Prevalence of Refractive Errors in the United States: The Multi-Ethnic Study of Atherosclerosis

Morphologic Characteristics of Optic Nerve Head Drusen on Spectral-Domain Optical Coherence Tomography

Visual Field Staging Systems in Glaucoma and the Activities of Daily Living

Reply

Atlas of Clinical and Surgical Orbital Anatomy, Second Edition

Color Atlas and Synopsis of Clinical Ophthalmology; Wills Eye Institute; Pediatric Ophthalmology

Retinoblastoma

Contents