American Journal of Ophthalmology - Articles in Press

Discrepancies between Fluorescein Angiography and Optical Coherence Tomography in Macular Edema in Uveitis - Corrected Proof

Jeannette Ossewaarde-Van Norel, Laurens P. Camfferman, Aniki Rothova — 2012-04-30

Purpose: To assess the frequency and characteristics of discrepant findings between fluorescein angiography (FA) and optical coherence tomography (OCT) in uveitic macular edema (ME). Design: Retrospective cross-sectional study of 112 eyes of 78 patients with uveitic ME on FA, OCT, or both. Methods: ME was graded on OCT and FA of uveitis patients attending the University Medical Center Utrecht. The frequency and severity of discrepant findings were analyzed, and the clinical findings at the time of imaging were assessed. The imaging studies were compared with the clinical characteristics. Results: Positive results of both imaging methods (FA+/OCT+) were observed in 61 (54%) of 112 eyes, whereas discrepant results occurred in 51 (46%) of 112 eyes. The FA+/OCT− discrepancy occurred in 34 (30%) of 112 eyes, and the FA−/OCT+ discrepancy occurred in 17 (15%) of 112 eyes. No correlations between the discrepant imaging results and age, gender, duration of uveitis or ME, visual acuity, or cause of uveitis were identified. FA+/OCT− and FA−/OCT+ discrepancies comprised typically mild degrees of ME. The FA+/OCT− discrepancy occurred in 50% of eyes with birdshot chorioretinopathy (7/14), and the FA−/OCT+ discrepancy occurred more often in intermediate uveitis than in other anatomic locations. Although the FA+/OCT+ consistency was noted frequently in active uveitis, the FA−/OCT+ discrepancy was common in eyes with inactive uveitis (8/18; 44% of inactive eyes). Conclusions: Our results emphasize that FA and OCT are complementary investigations, each revealing different aspects of the pathophysiology of uveitic ME.

Prediction of Proliferative Vitreoretinopathy after Retinal Detachment Surgery: Potential of Biomarker Profiling - Corrected Proof

2012-04-30

Purpose: To investigate the potential of a combined assessment of clinical risk factors and biomarker profiling in the prediction of proliferative vitreoretinopathy (PVR) after retinal detachment surgery. Design: Retrospective case-control study. Methods: Multiplex bead-based immunoassays were used for the simultaneous measurement of 50 biomarkers in subretinal fluid samples obtained from patients who underwent scleral buckling surgery for primary rhegmatogenous retinal detachment (RRD). Of 306 samples that were collected and stored in our BioBank, we selected 21 samples from patients in whom a redetachment developed as a result of PVR within 3 months after reattachment surgery for primary RRD (PVR group). These were compared with age-, sex-, and storage time-matched RRD samples from 54 patients with an uncomplicated postoperative course after primary RRD repair (RRD group). Results: Preoperative PVR was the only clinical variable that was an independent predictor of postoperative PVR development (P = .035) and resulted in an area under the receiver operating characteristic curve of 0.67 (95% confidence interval, 0.51 to 0.83). The addition of the biomarkers chemokine (C-C motif) ligand 22, interleukin-3, and macrophage migration inhibitory factor improved the model significantly (P < .001) and resulted in an area under the receiver operating characteristic curve of 0.93 (95% confidence interval, 0.82 to 1.04). A sensitivity of 94.1% and a specificity of 94.2% were reached, using a cutoff value of 5%. Conclusions: In combination with preoperative PVR grade, the measurement of a single biomarker or a small multibiomarker panel shows great potential and may predict postoperative PVR development after primary RRD in a highly sensitive and specific manner.

Long-term Outcomes of Vitrectomy for Progressive X-Linked Retinoschisis - Corrected Proof

2012-04-30

Purpose: To evaluate the long-term outcomes of vitrectomy for progressive X-linked retinoschisis. Design: Prospective, nonrandomized, consecutive, interventional case series. Methods: Twenty-eight eyes of 22 patients who were diagnosed with progressive X-linked retinoschisis were divided into 2 groups: a nonsurgical group (n = 11) and a vitrectomy group (n = 17). The main outcome measures included best-corrected visual acuity, the area of the macular schisis cavity measured by optical coherence tomography, the retinal anatomic status, and complications. Results: The mean follow-up period was 34.7 months (range, 10 to 68 months). The mean best-corrected visual acuity increased from 20/125 at baseline to 20/55 at the final follow-up in the vitrectomy group (P = .001), but decreased from 20/100 at baseline to 20/400 at the final follow-up in the nonsurgical group (P = .000). In the vitrectomy group, the macular schisis cavity resolved in all 17 eyes; the mean area of the macular schisis cavity decreased from 0.85 mm2 at baseline to 0.23 mm2 at the final follow-up (P = .000), and the retinas of 16 eyes (94%) were attached after surgery. In the nonsurgical group, retinal schisis progressively extended in 9 eyes (82%); the mean area of the macular schisis cavity increased from 0.82 mm2 at baseline to 1.21 mm2 at the final follow-up (P = .000); in 8 eyes (72%), retinal detachment developed, and 2 eyes (18%) experienced vitreous hemorrhage, which terminated the observations. Conclusions: Vitrectomy may be an effective and essential treatment for patients with progressive X-linked retinoschisis to prevent a deterioration of vision before severe complications developed in their eyes.

Development and Validation of a Standardized Tool for Reporting Retinal Findings in Abusive Head Trauma - Corrected Proof

Wai Siene Ng, Patrick Watts, Zoe Lawson, Alison Kemp, Sabine Maguire — 2012-04-30

Purpose: To develop and validate a robust standardized reporting tool for describing retinal findings in children examined for suspected abusive head trauma. Design: A prospective interobserver and intraobserver agreement study. Method: An evidence-based assessment pro forma was developed, recording hemorrhages (location, layer, severity) and additional features. Eight consultant pediatric ophthalmologists and 7 ophthalmology residents assessed a series of 105 high-quality RetCam images of 21 eyes from abusive head trauma cases with varying degrees of retinal hemorrhage and associated findings. The pediatric ophthalmologists performed a repeat assessment of the randomized images. The images were observed simultaneously with standardized display settings. Interobserver and intraobserver agreement was assessed using free-marginal multirater kappa, intraclass correlation coefficients, and concordance coefficients. Results: Almost-perfect interobserver agreement was observed for residents and pediatric ophthalmologists recording the presence and number of fundus hemorrhages (intraclass correlation coefficients 0.91 and 0.87, respectively) and the location of hemorrhages (concordance coefficients 0.86 and 0.85, respectively). Substantial agreement was observed by both groups regarding size of hemorrhage (concordance coefficients 0.73 and 0.76), moderate agreement for hemorrhage morphology (concordance coefficients 0.53 and 0.52), and other findings (concordance coefficients 0.48 and 0.59). Intraobserver agreement for pediatric ophthalmologists varied by question, ranging from substantial to perfect for the presence, number, location, size, and morphology of fundus hemorrhage. Conclusion: We have developed and validated a standardized clinical reporting tool for ophthalmic findings in suspected abusive head trauma, which has excellent interobserver and intraobserver agreement among consultant specialists and residents. We suggest that its use will improve standardized clinical reporting of such cases.

Depression, Post-traumatic Stress Disorder, and Dry Eye Syndrome: A Study Utilizing the National United States Veterans Affairs Administrative Database - Corrected Proof

2012-04-30

Purpose: To study the scope of dry eye syndrome (DES) in veterans on a national level and to evaluate the relationship between psychiatric diagnoses and DES. Design: Case-control study. Methods: Setting: Patients were seen in a Veterans Affairs (VA) eye clinic between 2006 and 2011. Patient population: Patients were divided into cases and controls with regard to their dry eye status (cases = ICD-9 code for DES plus dry eye therapy; controls = patients without ICD-9 code plus no therapy). Main outcome measures: The prevalence of DES and the influence of psychiatric diagnoses on the risk of DES. Results: A total of 2 454 458 patients were identified as either a dry eye case (n = 462 641) or control (n = 1 991 817). Overall, 19% of male patients and 22% of female patients had a diagnosis of DES, with female sex imparting an increased risk of DES at each decade compared to male sex (odds ratio [OR] 1.22–2.09). Several conditions were found to increase DES risk, including post-traumatic stress disorder (OR 1.92, 95% CI 1.91–1.94) and depression (OR 1.92, 95% CI 1.91–1.94) (analyses adjusted for sex and age). The use of several systemic medications was likewise associated with an increased risk of DES, including antidepressant medications (OR 1.97, 95% CI 1.79–2.17) and antianxiety medication (OR 1.74, 95% CI 1.58–1.91). Multivariate analysis (adjusted for age and sex) revealed that for psychiatric diagnoses, both the use of medication and the diagnosis remained significant risk factors when considered concomitantly, although the magnitude of each association decreased. Conclusions: DES is a disease associated with depression and post-traumatic stress disorder, and is prevalent among male and female veterans receiving eye care services. The association could be driven by underlying disease physiology or medications used to treat psychiatric conditions. Regardless of the causal link, this suggests that individuals with a known psychiatric diagnosis should be questioned about dry eye symptoms and, if applicable, referred to an eye care physician.

Intrachoroidal Cavitation in Macular Area of Eyes With Pathologic Myopia - Corrected Proof

2012-04-30

Purpose: To determine the incidence and characteristics of intrachoroidal cavitations in the macular area of eyes with high myopia. Design: Prospective, noninterventional case series. Methods: We evaluated 56 eyes of 44 patients with pathologic myopia (myopic spherical equivalent >8 diopters) and with patchy chorioretinal atrophy using a swept-source optical coherence tomographic (OCT) system with a center wavelength of 1050 nm. We focused on the changes in the scleral curvature in the area of patchy atrophy. The relationship of the macular intrachoroidal cavitation and retinoschisis was also analyzed. Sixty-eight consecutive patients with pathologic myopia but without patchy atrophy were analyzed as controls. Results: In 31 of 56 eyes (55.4%) with patchy atrophy, the swept-source OCT images showed that the sclera was bowed posteriorly in and around the patchy atrophy compared to neighboring sclera, whereas none of the 68 patients without patchy atrophy showed this finding. Macular intrachoroidal cavitation had OCT features similar to peripapillary intrachoroidal cavitation; the choroid in the macular intrachoroidal cavitation area appeared thickened and the retina was caved into the cavitation. There was a direct communication between the vitreous and intrachoroidal cavitation in 3 eyes. Retinoschisis was observed significantly more frequently in or around the patchy atrophy in eyes with macular intrachoroidal cavitation than in those without cavitation. Conclusions: These findings suggest that patchy atrophy affects the scleral contour within posterior staphyloma beyond the funduscopically identified patchy atrophy by macular intrachoroidal cavitation. Such deformation of sclera may facilitate the development of retinoschisis in and around the patchy atrophy.

Four-Year Incidence of Open-Angle Glaucoma and Ocular Hypertension: The Los Angeles Latino Eye Study - Corrected Proof

2012-04-30

Purpose: To estimate the 4-year incidence of open-angle glaucoma (OAG) and ocular hypertension (OHT) among adult Latinos 40 years of age and older. Design: Population-based longitudinal study. Methods: Comprehensive ophthalmologic examinations including intraocular pressure, visual field testing, and stereoscopic fundus photography were performed at both baseline and the 4-year follow-up examination. Incident OAG at the 4-year follow-up examination was defined as the presence of an open angle and a glaucomatous visual field abnormality or evidence of glaucomatous optic disc damage, or both when not present at baseline. Incident OHT was defined as intraocular pressure of more than 21 mm Hg and the absence of optic disc damage or abnormal visual field results at the 4 year follow-up examination when not present at baseline. Results: Among the 3939 participants (mean age, 54.7 ± 10.5 years) with complete data for a diagnosis of glaucoma at both baseline and follow-up examination, incident OAG at the 4-year follow-up was identified in 87 persons (4-year incidence rate, 2.3%; 95% confidence interval, 1.8% to 2.8%). Incident OHT at the 4-year follow-up was identified in 124 persons (4-year incidence rate, 3.5%; 95% confidence interval, 2.9% to 4.1%). In participants with OAG in 1 eye, the 4-year risk of OAG developing in the fellow eye was 5 times as high as the risk for those without OAG in either eye at baseline. In participants with OHT in 1 eye, the 4-year risk of OHT developing in the fellow eye was 10 times as high as the risk for those without OHT in either eye at baseline. The incidence rates of OAG and OHT were higher in older Latinos than in younger Latinos. Conclusions: Incidence of OAG in Latinos is higher than in non-Hispanic whites, but lower than in Afro-Caribbeans. The relatively high rate of incident OAG and OHT underscores the need for community screening programs in this fastest growing segment of the United States population.

Corneal Endothelial Morphologic Assessment in Pediatric Cataract Surgery with Intraocular Lens Implantation: A Comparison of Preoperative and Early Postoperative Specular Microscopy - Corrected Proof

2012-04-30

Purpose: To observe longitudinal changes in the corneal endothelium after pediatric cataract surgery with intraocular lens implantation. Design: Prospective, longitudinal study. Methods: settings: Iladevi Cataract and IOL Research Centre, Ahmedabad, India. study population: This study included 100 pediatric eyes undergoing cataract surgery with intraocular lens implantation. Posterior capsule management was based on the status of the posterior capsule. Two-port anterior limbal vitrectomy was carried out after posterior capsule plaque peeling. observation procedures: Corneal endothelial morphologic features: endothelial cell density (cell/mm2), coefficient of variation, percentage of hexagonality, and central corneal thickness were assessed. main outcome measures: To evaluate whether there is a difference in endothelial cell morphologic features before surgery and 3 months after surgery and also whether pediatric cataract surgery with and without anterior vitrectomy has any impact on the endothelial cell morphologic features. Results: A comparison of preoperative and postoperative specular microscopy is given here: endothelial cell density, 3225.1 ± 346.8 cells/mm2 versus 3057.7 ± 330.1 cells/mm2 (P < .001); coefficient of variation, 27.5 ± 10.6 versus 37.7 ± 16.3 (P < .001); percentage of hexagonality, 58.1 ± 15.3 versus 48.6 ± 13.4 (P < .001); and central corneal thickness, 529 ± 30 μm versus 527 ± 34 μm (P = .64). There was 5.1% decrease in mean endothelial cell loss at 3 months after surgery. No statistically significant difference was noted in the percentage decrease in mean endothelial cell density between eyes undergoing cataract surgery with intact posterior capsules, eyes undergoing manual posterior capsulorrhexis without anterior limbal vitrectomy, and eyes undergoing anterior limbal vitrectomy (P = .543). Conclusions: Endothelial cell loss with currently practiced techniques of pediatric cataract surgery is within acceptable limits by adhering to the principles of close chamber technique.

Responses to Photodynamic Therapy in Patients With Polypoidal Choroidal Vasculopathy Consisting of Polyps Resembling Grape Clusters - Corrected Proof

Won Ki Lee, Kyu Seop Kim, Wungjae Kim, Seung Bum Lee, Sohee Jeon — 2012-04-30

Purpose: To investigate the responses to photodynamic therapy (PDT) in patients with polypoidal choroidal vasculopathy (PCV) that show large aneurysmal dilation with internal angio-architecture consisting of diverse patterns of curvilinear vessels and polyps resembling grape clusters. Design: Retrospective, interventional case series. Methods: Twenty-two eyes of 22 patients were included. All patients initially received PDT monotreatment. The main outcome measures were the rates of complete polyp regression on indocyanine green angiography and initial favorable responses observed clinically. Also, the rates of recurrent exudative changes were evaluated at the 2-year follow-up. We focused on changes in the vascular features and their clinical association. Results: Complete regression of polypoidal lesions was observed in 21 eyes (95%) after a mean of 1.7 PDTs. However, favorable clinical responses were achieved in only 9 eyes (41%), and 6 of them had recurrent exudation. Main vessels, previously consisting of the polypoidal lesion frame, persisted. Additionally, aberrant vessels with a thin radiating or tortuous configuration were observed in the area where large aneurysmal dilation was present. Leakage from this vascular complex or an expanded vascular complex was observed in a total of 14 eyes (64%) during the 2-year follow-up, contributing to persistent (8 eyes) or recurrent (6 eyes) exudation. This seemed to represent secondary choroidal neovascularization (CNV). In another 4 eyes (18%), fibrous changes developed immediately after PDT. Polyps recurred in 8 eyes (38%). Conclusions: This PCV pattern frequently evolved into typical CNV after PDT, resulting in persistent or recurrent exudation despite the disappearance of polypoidal structures.

Anti-inflammatory Effect of Low-Molecular-Weight Heparin in Pediatric Cataract Surgery: A Randomized Clinical Trial - Corrected Proof

2012-04-30

Purpose: To determine if intraocular infusion of low-molecular-weight heparin (enoxaparin) reduces postoperative inflammation in pediatric eyes undergoing cataract surgery with IOL implantation. Design: Prospective masked randomized controlled trial. Methods: Setting: Private, institutional practice. Study population: Twenty children (40 eyes) undergoing bilateral cataract surgery with IOL implantation were randomized to receive enoxaparin in the intraocular infusion fluid (BSS) (Group I) or not to receive enoxaparin (Group II). The first eye was randomly assigned to 1 of the 2 groups and the second eye received alternate treatment. Observation procedure: Patients were followed up in the first week and 1 and 3 months after surgery. Main outcome measures: Anterior chamber flare and cells (Hogan's criteria), cell deposits on IOL, posterior synechiae. Results: One week postoperatively, no eyes had >grade 2 flare/cells. Proportion of eyes with grade 2 cells was higher in eyes that did not receive enoxaparin (Group II: 80% vs Group I: 40%, P = .009). In the first week >10 small cell deposits were noted in the eyes that received enoxaparin (Group I: 20%, Group II: none, P = .005). Large cell deposits first appeared at 1 month in 40% of eyes in Group I and 55% of eyes in Group II (P = .34) and increased at 3 months (60% in both groups, P > .999). Posterior synechiae were seen in 10% of eyes in Group I at 1 month, which persisted at 3 months; no eyes in Group II showed posterior synechiae (P = .14). Conclusion: The results of our study suggest that there does not seem to be a benefit of using enoxaparin in the infusion fluid with respect to early postoperative inflammation.

Uveal Melanoma: Molecular Pattern, Clinical Features, and Radiation Response - Corrected Proof

2012-04-30

Purpose: To characterize the clinical spectrum of class 1 and class 2 uveal melanomas and their relationship with intraocular proton radiation response. Design: Masked retrospective case series of uveal melanoma patients with fine needle biopsy–based molecular profiles. Methods: A total of 197 uveal melanoma patients from a single institution were analyzed for pathology, clinical characteristics, and response to radiation therapy. Results: A total of 126 patients (64%) had class 1 tumors and 71 (36%) had class 2 tumors. Patients with class 2 tumors had more advanced age (mean: 64 years vs 57 years; P = .001), had thicker initial mean ultrasound measurements (7.4 mm vs 5.9 mm; P = .0007), and were more likely to have epithelioid or mixed cells on cytopathology (66% vs 38%; P = .0004). Although mean pretreatment and posttreatment ultrasound thicknesses were significantly different between class 1 and class 2 tumors, there was no difference in the mean change in thickness 24 months after radiation therapy (mean difference: class 1 = −1.64 mm, class 2 = −1.47; P = .47) or in the overall rate of thickness change (slope: P = .64). Class 2 tumors were more likely to metastasize and cause death than class 1 tumors (DSS: P < .0001). Conclusions: At the time of radiation therapy, thicker tumors, epithelioid pathology, and older patient age are significantly related to class 2 tumors, and class 2 tumors result in higher tumor-related mortality. We found no definitive clinical marker for differentiating class 1 and class 2 tumors.

Economic Evaluation of Endothelial Keratoplasty Techniques and Penetrating Keratoplasty in The Netherlands - Corrected Proof

2012-04-30

Purpose: To evaluate cost-effectiveness of penetrating keratoplasty (PK), femtosecond laser-assisted Descemet stripping endothelial keratoplasty (FS-DSEK), and Descemet stripping automated endothelial keratoplasty (DSAEK). Design: Cost-effectiveness analysis based on data from a randomized multicenter clinical trial and a noncomparative prospective study. Methods: Data of 118 patients with corneal endothelial dysfunction were analyzed in the economic evaluation. Forty patients were included in the PK group, 36 in the FS-DSEK group, and 42 in the DSAEK group. The primary incremental cost-effectiveness ratio (ICER) was the incremental costs per clinically improved patient, defined as a patient with a combined effectiveness of both a clinically improved BSCVA (defined as an improvement of at least 2 lines) and a clinically acceptable refractive astigmatism (defined as less than or equal to 3.0 diopters). Analysis was based on a 1-year follow-up period after transplantation. Results: The percentage of treated patients who met the combined effectiveness measures was 52% for DSAEK, 44% for PK, and 43% for FS-DSEK. Mean total costs per patient were €6674 (US$7942), €12 443 (US$14 807), and €7072 (US$8416) in the PK group, FS-DSEK group, and DSAEK group, respectively. FS-DSEK was less effective and more costly compared to both DSAEK and PK. DSAEK was more costly but also more effective compared to PK, resulting in incremental costs of €4975 (US$5920) per additional clinically improved patient. Conclusions: The results of this study show that FS-DSEK was not cost-effective compared to PK and DSAEK. DSAEK, on the other hand, was more costly but also more effective compared to PK. Including societal costs, a longer follow-up period and preparation of the lamellar transplant buttons in a national cornea bank could improve the cost-effectiveness of DSAEK.

The Changing Face of Primary Open-Angle Glaucoma in the United States: Demographic and Geographic Changes From 2011 to 2050 - Corrected Proof

Thasarat S. Vajaranant, Shuang Wu, Mina Torres, Rohit Varma — 2012-04-30

Purpose: To examine how demographic and geographic variations in US populations from 2011 to 2050 will contribute to estimated numbers of primary open-angle glaucoma (POAG) cases. Design: Cross-sectional study. Methods: Prevalence rates from selected population-based studies were used to estimate the number of persons aged 40 years and older with POAG in the United States. For calculation, the age-, sex-, and race/ethnicity-specific prevalence rates were multiplied by the US Census estimates and projections from 2011 to 2050. Main outcome measures are estimated numbers of persons with POAG in different age, sex, and racial/ethnic groups and total and per capita POAG rates by state. Results: In 2011, 2.71 million persons in the United States have POAG, with the highest estimated number among populations aged 70 to 79 years (31%), women (53%), and non-Hispanic whites (44%). The largest demographic group is non-Hispanic white women. In 2050, an estimated 7.32 million persons will have POAG, with the highest number among populations aged 70 to 79 years (32%), women (50%), and Hispanics (50%). The largest demographic group will shift to Hispanic men. During the next 40 years, the highest per capita POAG rates will double in New Mexico, Texas, and Florida. Conclusions: Despite the high prevalence of POAG in African Americans and Hispanics, the largest group in the United States is currently among older non-Hispanic white women but is expected to shift to Hispanic men over the next few decades. Given this shift, the greatest yield from screening programs is likely to be in those states with high numbers of non-Hispanic white women and Hispanic men.

Improvement of Photoreceptor Integrity and Associated Visual Outcome in Neovascular Age-Related Macular Degeneration - Corrected Proof

Yong Min Kim, Ji Hyun Kim, Hyoung Jun Koh — 2012-04-27

Purpose: To evaluate the association between improvement of photoreceptor integrity and visual acuity (VA) after anti–vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (AMD). Design: Retrospective, cross-sectional study. Methods: Eighty-seven eyes of 84 patients who were newly diagnosed with neovascular AMD and treated with anti-VEGF injections were reviewed retrospectively. Using spectral-domain optical coherence tomography, the status of the inner segment/outer segment photoreceptor junction (IS/OS) was graded and classified into 3 groups at baseline and 1 and 2 months after 3 monthly injections. The proportion of the improved IS/OS line after treatment was analyzed and correlated with VA. Results: The number of eyes in the IS/OS+ group, representing disrupted IS/OS line less than 200 μm, was increased from 9 (10%) at baseline to 33 (38%) at 1 month. There was a significant difference in the ratio of IS/OS+ group between baseline and 1 month (P < .001). Those in the IS/OS± group, showing focal disrupted IS/OS line between 200 and 800 μm, decreased from 29 (33%) to 22 eyes (25%). Improvement of the IS/OS line at 1 month compared to baseline was noted in 43 eyes (49%) and correlated with better VA (P < .016). No increase of VA was observed in 44 eyes without definite improvement. There was no significant correlation between improvement of the IS/OS line and VA from 1 to 2 months. Conclusions: Assessing the change of the photoreceptor integrity before and after treatment would be a useful indicator to predict initial response to treatment and visual prognosis in patients with neovascular AMD.

Morphometric Spectral-Domain Optical Coherence Tomography Features of Epiretinal Membrane Correlate with Visual Acuity in Patients with Uveitis - Corrected Proof

2012-04-27

Purpose: To identify visually significant spectral-domain optical coherence tomography (SD-OCT) features of epiretinal membranes (ERM) in patients with uveitis. Design: Retrospective cohort and cross-sectional study. Methods: Eighty consecutive eyes with uveitis and SD-OCT–documented ERM were included. Clinical data were collected at the time of diagnosis of ERM and at the final visit. SD-OCT images at the last visit were evaluated to identify fovea and ERM configuration and structural changes. Changes of 10% and 20% in central subfield thickness between initial and last SD-OCT were calculated and correlated with visual acuity (VA). An ERM thickness map was created using validated SD-OCT grading software. Results: VA improved significantly in eyes with more than 12 months of follow-up (P = .03). Although inflammation activity and medical treatment methods were no different in eyes with more or less than 12 months of follow-up, 16 eyes in the subset with longer follow-up underwent cataract extraction and intraocular lens implantation. Kaplan-Meier analysis demonstrated few vision losses during the follow-up period. Change in central subfield thickness did not correlate with VA. Foveal center involvement (P < .001), focal attachment of the ERM (P = .003), and foveal inner segment and outer segment junction disruption (P = .006) were associated independently with lower VA. ERM was thinner in eyes with 20/40 or better VA (4.6 ± 0.6 μm) compared with eyes with VA of less than 20/200 (P = .02). Longer duration of ERM was associated with thicker ERM (P < .05). Conclusions: In most eyes with uveitis and ERM, VA remains stable if ocular inflammation and comorbidities are addressed appropriately.

The Impact of Cataract, Cataract Types, and Cataract Grades on Vision-Specific Functioning Using Rasch Analysis - Corrected Proof

2012-04-27

Purpose: To determine the impact of cataracts and their types and grades on vision-specific functioning. Design: Prospective population-based cross-sectional study. Methods: The Singapore Indian Eye Study examined 3400 of 4497 (75.6% response rate) ethnic Indians 40 years of age and older living in Singapore. Three thousand one hundred sixty-eight (93.2%) fulfilled inclusion criteria with complete information for final analysis. Cataracts were assessed on slit-lamp examination and were graded according to the Lens Opacity Classification System III. Vision-specific functioning scores were explored with the Visual Function scale, validated using Rasch analysis. Results: Two hundred sixty-nine (8.5%) and 740 (23.4%) of the study participants had unilateral and bilateral cataracts, respectively, and 329 (10.4%), 800 (25.2%), and 128 (4.1%) participants had nuclear, cortical, and posterior subcapsular (PSC) cataracts, respectively. In multivariate linear regression models, the presence of bilateral rather than unilateral cataract (β = −0.12; 95% confidence interval, −0.20 to 0.00) was associated independently with poorer vision-specific functioning, even after adjusting for undercorrected refractive error (β = −0.11; 95% confidence interval, −0.21 to 0.00). Bilateral nuclear, cortical, and PSC cataracts also were associated with poorer vision-specific functioning (β = −0.31, −0.15, and −1.15, respectively), with combinations of them having even greater impact. Significantly poorer vision-specific functioning occurred at Lens Opacity Classification System grades 4 (nuclear opalescence), 5 (nuclear color), 3 (cortical), and 1 (PSC) or higher. Conclusions: People with bilateral but not unilateral cataracts experience difficulty with performing vision-specific daily activities independent of refractive error, with PSC cataracts and cataract combinations having the greatest impact. Cataract types cause poorer vision-specific functioning beginning at different severity grades.

Efficacy of Topical Blockade of Interleukin-1 in Experimental Dry Eye Disease - Corrected Proof

Andre Okanobo, Sunil K. Chauhan, Mohammad H. Dastjerdi, Shilpa Kodati, Reza Dana — 2012-04-27

Purpose: To evaluate the therapeutic efficacy of topical interleukin-1 receptor antagonist (IL-1Ra) in the treatment of dry eye disease. Design: Laboratory investigation. Methods: Dry eye disease was induced in C57BL/6 female mice through exposure to a desiccating environment within a controlled environment chamber. Topical formulations containing 5% IL-1Ra, 1% methylprednisolone, 0.05% cyclosporin A, and a vehicle control containing carboxymethylcellulose sodium were applied after the induction of dry eye. Corneal fluorescein staining was performed by a masked observer in the different treatment groups. Immunohistochemical studies were undertaken to enumerate corneal CD11b+ cells, as well as to evaluate corneal lymphangiogenesis. Real-time polymerase reaction was used to quantify the expression of interleukin-1β in the cornea. Results: A significant decrease in corneal fluorescein staining was observed after topical treatment with 5% IL-1Ra (P < .01), 1% methylprednisolone (P < .01), and 0.05% cyclosporin A (P < .03). Additionally, a significant decrease in the numbers of central corneal CD11b+ cells (P < .05), corneal lymphatic growth (P < .05), and corneal interleukin-1β expression (P < .003), compared with vehicle treated, were demonstrated only after treatment with 5% IL-1Ra and 1% methylprednisolone, and were absent after cyclosporin A treatment. Conclusions: Topical treatment with IL-1Ra is effective in ameliorating the clinical signs of the dry eye disease, as well as in reducing underlying inflammation. These effects are comparable with those resulting from treatment with topical methylprednisolone. Topical IL-1Ra may hold promise as a novel therapeutic strategy in the treatment of dry eye.

Enhanced Circulating Soluble LR11 in Patients with Diabetic Retinopathy - Corrected Proof

2012-04-27

Purpose: To investigate the relationship of circulating levels of soluble form of LR11 (sLR11; also called SorLA or SORL1), with the progression of proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus. Design: Cross-sectional study. Methods: Fifty-four patients with type 2 diabetes mellitus were divided into 2 sex- and age-matched groups: one with PDR (n = 29) and the other with nonproliferative diabetic retinopathy (n = 25). The serum sLR11 levels were measured with an immunodetection system followed by chemifluorescence quantification. Results: The serum sLR11 levels were higher in the PDR group than in the nonproliferative diabetic retinopathy group (5.8 ± 1.2 U vs 3.7 ± 1.3 U; P < .01). A multivariate regression analysis showed that circulating sLR11 is a factor contributing to the prediction of PDR independent of other classical risk factors, and an area under the receiver operating characteristic curve analysis revealed that the sensitivity and the specificity were equivalent to or more than those of other factors. Among the classical risk factors for PDR, glycosylated hemoglobin levels showed the highest correlation coefficient (P < .01) for the sLR11 concentrations. Conclusions: Serum sLR11 concentration may reflect the progression of PDR in patients with type 2 diabetes mellitus. sLR11, released from immature vascular cells and indicating the development of atherosclerosis, is expected to be a novel candidate biomarker indicating diabetic retinopathy in patients with type 2 diabetes mellitus.

Altered Expression of CD46 and CD59 on Leukocytes in Neovascular Age-Related Macular Degeneration - Corrected Proof

2012-04-27

Purpose: To investigate the expression of the complement regulatory proteins CD46, CD55, and CD59 on peripheral leukocytes in neovascular age-related macular degeneration (AMD). Design: Prospective, case-control study. Methods: Thirty-five unrelated patients with neovascular AMD and 30 control individuals were included in this case-control study. All participants were subjected to a structured interview and detailed imaging (autofluorescence, digital funduscopy, spectral-domain optical coherence tomography, and fluorescein and indocyanine green angiography in patients suspected of having neovascular AMD) was performed. Fresh ethylenediamine-tetraacetic acid blood was obtained and stained with monoclonal antibodies. Using flow cytometry, the percentage of CD14+ monocytes, CD45+ lymphocytes, and CD45+ granulocytes positive for CD46, CD55, and CD59 was determined in patients with neovascular AMD and was compared with that of controls. Results: We found that the expression of CD46 and CD59 was significantly lower on CD14+ monocytes in patients with neovascular AMD compared with controls (P = .0070). A significantly lower expression of CD46 on lymphocytes was observed in patients with fibrosis compared with patients without fibrosis (P = .010). Conclusions: Our study suggests that neovascular AMD is associated with an inadequate regulation of the complement system, supporting current evidence on the role of complement dysregulation in the pathogenesis of AMD.

Scalability and Severity of Keratoconus in Children - Corrected Proof

2012-04-25

Purpose: To assess the severity of keratoconus at diagnosis and its scalability over a period of 2 years in children compared to adults. Design: A retrospective monocentric study was conducted in the National Reference Center for Keratoconus, Bordeaux (France), between October 1997 and November 2010. Methods: In total, 216 patients were studied, comprising 49 patients (22.7%) aged ≤15 and 167 patients (77.3%) aged ≥27 years at diagnosis, who were seen within 2 years of diagnosis. Severity at diagnosis was assessed using Krumeich's classification, and the scalability criteria of the US Food and Drug Administration (2010) were used. Student t tests and χ2 tests were performed to compare the 2 groups. Results: Keratoconus in children was significantly more severe at diagnosis, with 27.8% being stage 4 vs 7.8% of adults (P < .0001). In addition, ophthalmoscopic signs were more frequent in children (42.9% vs 29.5%, P = .05), while mean values of maximum, average, and minimum keratometry as well as simulated keratometric astigmatism were higher (P < .0001, P = .0002, P = .0005, and P = .001, respectively). After diagnosis, keratoconus did not evolve more frequently in children. However, in the case of progression, keratoconus evolved faster in children, with significant differences in the spherical equivalent and maximum and minimum keratometry (P = .03, P = .02, P = .04, respectively). Conclusion: At diagnosis, keratoconus is often more advanced in children than in adults, with faster disease progression. Early detection and close monitoring are therefore crucial in young patients.

Prevalence and Correction of Near Vision Impairment at Seven Sites in China, India, Nepal, Niger, South Africa, and the United States - Corrected Proof

2012-04-25

Purpose: To estimate the prevalence of near vision impairment and use of corrective spectacles among middle-aged and older adults in different settings and ethnic groups. Design: Population-based, cross-sectional study. Methods: People aged ≥35 years were randomly selected with cluster sampling in 4 rural settings in Shunyi (China), Kaski (Nepal), Madurai (India), and Dosso (Niger); 1 semi-urban area in Durban (South Africa); and 2 urban settings in Guangzhou (China) and Los Angeles (USA). Near visual acuity (VA), with and without presenting near correction, was measured at 40 cm using a logMAR near vision tumbling E chart. Subjects with uncorrected binocular near VA ≤20/40 were tested with plus spheres to obtain the best-corrected binocular VA. Results: A total of 17 734 persons aged ≥35 years were enumerated and 14 805 (83.5%) were examined. The age- and sex-standardized prevalence of uncorrected near vision impairment (VA ≤20/40) ranged from 49% in Dosso to 60% in Shunyi and Guangzhou, 65% in Kaski and Los Angeles, and 83% in Madurai and Durban. The prevalence of near vision impairment based on best-corrected visual acuity was less than 10% in Guangzhou, Kaski, Durban, and Los Angeles, but as high as 23% in Madurai. In multiple logistic regression models, uncorrected near vision impairment was associated with older age (odds ratio [OR] = 1.14, P < .001) and female sex (OR = 1.12, P = .027), but not with educational level (OR = 1.01, P = .812). Over 90% of people in need of near refractive correction in rural settings did not have the necessary spectacles. These rates were 40% in urban settings. Conclusions: By 50 years of age, the majority of people suffer from near vision impairment, most of which can be corrected optically. Over 90% of those in need of near refractive correction in rural settings do not have the necessary spectacles.

Photoreceptor Damage and Foveal Sensitivity in Surgically Closed Macular Holes: An Adaptive Optics Scanning Laser Ophthalmoscopy Study - Corrected Proof

2012-04-25

Purpose: To assess photoreceptor structure using adaptive optics scanning laser ophthalmoscopy (AO SLO) and spectral-domain optical coherence tomography (SD OCT) and to evaluate the relationship between structural abnormalities and foveal sensitivity in eyes with surgically closed macular hole (MH). Design: Prospective, interventional case series. Methods: Twenty-one eyes of 19 patients with idiopathic MH underwent a full ophthalmologic examination, including SD OCT at baseline. Imaging with SD OCT, an original prototype AO SLO system, and microperimetry were performed at 6 months after surgery. Results: All patients underwent anatomically successful MH closure. On AO SLO, dark areas (0.004 to 0.754 mm2) were seen in all eyes after MH repair. Lower cone density correlated with poorer postoperative visual acuity and lower mean foveal sensitivity (both P < .001). Larger dark areas on AO SLO correlated with poorer postoperative visual acuity (P = .003) and lower mean foveal sensitivity (P = .006). Cone density was significantly lower and dark areas were significantly larger in eyes that had defects of the outer segments in the fluid cuff before surgery (P = .018 and P = .001, respectively) and moderately reflective foveal lesions after surgery (P < .001 and P < .001, respectively). Larger dark areas correlated with longer symptom duration before surgery (P < .001). Conclusions: Structural damage to the photoreceptor layer correlated with greater decreases in visual function in eyes with surgically closed MH. AO SLO imaging is a useful and quantitative tool for detecting photoreceptor abnormalities and their association with visual acuity and retinal sensitivity in eyes with closed MH.

The Distribution of Intraocular Pressure in Urban and in Rural Populations: The Namil Study in South Korea - Corrected Proof

Wool Suh, Changwon Kee, Namil Study Group and Korean Glaucoma Society — 2012-04-16

Purpose: To evaluate the intraocular pressure (IOP) distribution and its regional association in the South Korean population. Design: Cross-sectional, epidemiologic study. Methods: All participants underwent interview and the following ocular examinations: visual acuity measurement, autorefraction, pachymetry, anterior segment evaluation, slit-lamp examination, Goldmann applanation tonometry, binocular optic disc evaluation, fundus photography, and visual field test. Patients with ocular diseases other than mild senile cataract or with history of ocular surgery were excluded. Results: A total of 3191 subjects residing in urban and rural areas were recruited. Mean IOP of patients from the urban area was significantly higher than that of those from the rural area (14.45 ± 2.67 mm Hg vs 13.53 ± 2.76 mm Hg, P < .05). There was regional difference of mean IOP, even after controlling for different demographic factors in the 2 areas (P < .05). Average IOP in the right eye of the investigated sample of South Korean population was 14.10 ± 2.74 mm Hg. Multiple regression analysis showed positive correlation between mean IOP and central corneal thickness, vertical cup-to-disc ratio, history of hypertension, smoking, and female sex, whereas IOP tended to decrease by approximately 0.2 mm Hg when age increased by 10 years. Conclusions: This is the first population-based epidemiologic study measuring IOP in the South Korean population. Mean IOP of the urban area was found to be significantly higher than the corresponding value of the rural area. Therefore, the regional difference, as well as other various factors, has to be considered in epidemiologic study of the distribution of IOP.

Diffuse Large B-Cell Lymphoma of the Orbit: Clinicopathologic, Immunohistochemical, and Prognostic Features of 20 Cases - Corrected Proof

2012-04-16

Purpose: To evaluate a series of orbital diffuse large B-cell lymphomas (DLBCL) for prognostic features and therapeutic outcomes. Design: Retrospective multicenter case study of clinical and immunohistochemical features of 20 patients. Methods: Clinical, histopathologic, and immunohistochemical features were correlated with outcomes. Immunohistochemistry for biomarkers including Bcl-6, CD5, CD10, CD20, FOXP1, GCET1, and MUM1 was performed to differentiate between 2 major genetic subtypes of DLBCL: activated B-cell-like (ABC) and germinal center B-cell-like (GCB). Results: Sixteen patients presented with unilateral and 4 with bilateral tumors. Three had bony erosion of the orbit on imaging studies. Of 14 patients with detailed follow-ups, 3 had a prior or concurrent lymphomatous disease; 8 had stage I disease (limited to the orbit) at presentation; and 3 were newly diagnosed with systemic (stage IV) DLBCL. Localized disease was treated with combined systemic chemotherapy, including rituximab and radiation with no deaths to date; there was 1 death related to systemic DLBCL. Clinical staging was the best predictive method and no immunohistochemical feature or subcategory (ABC vs GCB) correlated with outcome. Conclusions: Primary orbital DLBCL has a more favorable prognosis than systemic DLBCL and may arise from a preexistent hematolymphomatous neoplasm (4 out of 20 cases). In our series, orbital DLBCL had a 57% likelihood of being restricted to the ocular adnexa. Clinical staging was more helpful in predicting outcome than any single immunohistopathologic feature or combination of biomarkers. Orbital radiation of 30 gray in conjunction with systemic chemotherapy with rituximab can achieve disease-specific survival approaching 100% in purely localized cases.

Retro-mode Imaging for Retinal Pigment Epithelium Alterations in Central Serous Chorioretinopathy - Corrected Proof

Yong Un Shin, Byung Ro Lee — 2012-04-16

Purpose: To propose a simple, noninvasive retro-mode imaging technique employing confocal scanning laser ophthalmoscopy (cSLO) as a novel imaging modality for the detection of alterations in retinal pigment epithelium (RPE) in central serous chorioretinopathy (CSCR). Design: Retrospective observational case series. Methods: A total of 48 eyes from 45 patients at various phases of CSCR were included. All patients underwent spectral-domain optical coherence tomography (SD-OCT) using a volume scan protocol, fluorescein angiography (FA), indocyanine green angiography (IA), and retro-mode imaging by cSLO. We investigated retro-mode images to evaluate RPE status by comparing the results with those of SD-OCT, FA, and IA. Results: Patients had various phases of CSCR: acute (23 eyes), chronic (17 eyes), and resolved (8 eyes). Retro-mode imaging detected subtle alterations in subretinal fluid (SRF) and RPE, which were undetectable with FA or IA. The correspondence between SD-OCT scanning the entire macula and retro-mode imaging differed according to the chronicity of the disease. In cases with acute CSCR, the correspondence with SD-OCT reached 44.44% in eyes with semicircular pigment epithelial detachment (PED), 33.33% in eyes with low to flat PED, and 35.71% in eyes with RPE protrusion. In cases with chronic CSCR, the correspondence with SD-OCT reached 83.33%, 57.14%, and 85.71% in eyes with semicircular PED, low to flat PED, and RPE protrusion, respectively. Correspondence in cases with resolved CSCR was 100% in eyes with either semicircular or low to flat PED and 83.33% in eyes with RPE protrusion. Conclusions: Simple and noninvasive retro-mode imaging by cSLO provides improved comprehensive topographic information of RPE alterations in CSCR. Our detailed interpretation may be useful for future research of retro-mode imaging in various macular disorders.

Second-generation Trabecular Meshwork Bypass Stent (iStent inject) Increases Outflow Facility in Cultured Human Anterior Segments - Corrected Proof

2012-04-01

Purpose: To determine whether a second-generation trabecular meshwork (TM) bypass stent (iStent inject) influences outflow facility in cultured human anterior segments. Design: Prospective laboratory investigation using normal human donor eyes. Methods: Human anterior segments (n = 7) were placed in perfusion organ culture. One or 2 iStent inject stents were inserted into the TM within the nasal and/or superior quadrants using a specially designed injector. Anterior segments were returned to culture and perfused for an additional 24 hours. Morphology of the TM and Schlemm canal (SC) was assessed by scanning electron microscopy (SEM) and 3-dimensional micro-computed tomography (3D micro-CT). Results: Insertion of 1 iStent inject into the nasal or superior quadrant of the TM increased outflow facility from 0.16 ± 0.05 μL/min/mm Hg to 0.38 ± 0.23 μL/min/mm Hg (P < .03, n = 7), with concurrent pressure reduction from 16.7 ± 5.4 mm Hg to 8.6 ± 4.4 mm Hg. Addition of a second iStent inject further increased outflow facility to 0.78 ± 0.66 μL/min/mm Hg (n = 2). SEM showed the iStent inject flange compressed against the uveal region of the TM, the thorax securely inserted within the TM, and the head located in the lumen of SC. Dilation of SC was noted around the iStent inject head and SC cell disruption was observed at the iStent inject insertion site. 3D micro-CT confirmed iStent inject placement. Conclusion: iStent inject, a second-generation bypass stent, increased outflow facility in human anterior segment culture. The iStent inject is a promising new device to lower intraocular pressure via TM bypass.

Subconjunctival Sirolimus for the Treatment of Chronic Active Anterior Uveitis: Results of a Pilot Trial - Corrected Proof

2012-04-01

Purpose: To evaluate the safety and possible efficacy of subconjunctival sirolimus for the treatment of chronic active anterior uveitis. Design: Prospective, nonrandomized, open-label clinical trial. Methods: This single-center pilot trial enrolled 5 patients with chronic active anterior uveitis. The study drug was administered as a single subconjunctival injection of 30 μL (1320 μg) sirolimus in the study eye at the baseline visit. Study visits were performed at baseline, at 2 weeks, at 4 weeks, and monthly until 4 months, and included a complete ophthalmic examination, review of systems, adverse event assessment at each visit, physical examination, and ancillary ophthalmic testing at some visits. The primary outcome measure was a 2-step reduction in the anterior chamber inflammation within 4 weeks of injection of the study drug. Results: There were 3 female and 2 male patients; 4 patients had idiopathic anterior uveitis and 1 had psoriatic arthritis-associated anterior uveitis. Three of the 5 patients met the primary outcome criteria by showing at least a 2-step decrease in inflammation within 4 weeks; 2 patients showed a 1-step decrease in inflammation within the same time frame. No recurrence was encountered during a 4-month follow-up. There were no serious adverse events. Conclusions: Subconjunctival sirolimus appears to be well tolerated in this pilot trial and shows promise as a treatment for active inflammation in patients with chronic anterior uveitis. Larger studies are needed to assess its usefulness in uveitis.

One-Year Results of Three Monthly Ranibizumab Injections and As-Needed Reinjections for Polypoidal Choroidal Vasculopathy in Japanese Patients - Corrected Proof

2012-04-01

Purpose: To investigate the 1-year outcomes of monthly intravitreal injections of ranibizumab for 3 months followed by an as-needed reinjection schedule to treat polypoidal choroidal vasculopathy (PCV) in Japanese patients. Design: Prospective, consecutive case series. Methods: Eighty-five eyes of 82 consecutive Japanese patients with naïve symptomatic PCV received monthly intravitreal injections of ranibizumab for 3 months followed by an as-needed reinjection schedule. Eighty-one eyes (95%) followed for 1 year were studied. Results: A mean of 4.2 ± 1.3 (mean ± standard deviation) injections were administered over 1 year. Twenty-three of 81 eyes (28%) did not require additional injections and 32 eyes (40%) required only 1 injection after the 3 monthly injections. The mean (± standard error) logarithm of minimal angle of resolution (logMAR) visual acuity (VA) at baseline was 0.59 ± 0.37 and improved to 0.37 ± 0.30 (P = .001). Thirty eyes (37%) and 5 eyes (6%), respectively, had improved and decreased VA of 0.3 or more logMAR unit. Indocyanine green angiography showed that the polypoidal lesions resolved in 21 eyes (26%) and 32 eyes (40%) 3 months and 1 year after the first injection, respectively. Abnormal choroidal vessels remained in all eyes. Conclusions: Monthly injections of ranibizumab for 3 months to treat PCV improved the VA, and a reinjection schedule based on need maintained the improved VA. The polypoidal lesions tended to improve over 1 year, whereas abnormal choroidal vessels remained in all eyes. Further long-term follow-up is needed to determine the efficacy of ranibizumab therapy for PCV.

Treatment of Serous Macular Detachment Associated With Circumscribed Choroidal Hemangioma - Corrected Proof

Hee Jung Kwon, Min Kim, Christopher Seungkyu Lee, Sung Chul Lee — 2012-04-01

Purpose: To evaluate the effects of transpupillary thermotherapy and intravitreal bevacizumab injection on serous macular detachment and cystoid macular edema (CME) associated with circumscribed choroidal hemangioma. Design: Retrospective, interventional case series. Methods: We reviewed the records of 12 patients with circumscribed choroidal hemangioma treated with transpupillary thermotherapy and/or intravitreal injection of bevacizumab. We assessed changes in best-corrected visual acuity (BCVA), central foveal thickness by optical coherence tomography, and resolution of serous macular detachment and CME. Results: Six of 8 patients treated with transpupillary thermotherapy showed complete resolution of serous macular detachment and CME and the median minimal angle of resolution (logMAR) BCVA improved from 0.85 to 0.35 (P = .026). Among these 6 patients, 1 had no recurrence for 86 months and 5 had sustained resolution of serous macular detachment for a mean duration of 32.8 months before recurrence. Among the 9 patients treated with bevacizumab (including 5 patients who had transpupillary thermotherapy as a primary treatment), 5 showed resolution of serous macular detachment and the median logMAR BCVA improved from 0.7 to 0.5 (P = .042). Among these 5 patients, 3 had sustained resolution for a mean duration of 5.7 months and 2 showed recurrent serous macular detachment after 3 and 12 months. Conclusion: Transpupillary thermotherapy and intravitreal bevacizumab appear effective in the management of symptomatic circumscribed choroidal hemangioma, although recurrence of serous macular detachment and CME developed after long-term follow-up of transpupillary thermotherapy, and the duration of treatment effectiveness appears to be short with bevacizumab.

Factors Associated With the Response of Age-Related Macular Degeneration to Intravitreal Ranibizumab Treatment - Corrected Proof

2012-04-01

Purpose: To investigate factors affecting patient response to intravitreal ranibizumab treatment for age-related macular degeneration (AMD). Design: Retrospective chart review. Methods: We reviewed medical records of 105 consecutive eyes with AMD treated with intravitreal ranibizumab injections and followed for more than 1 year after treatment. Response to ranibizumab treatment was compared between typical neovascular AMD and polypoidal choroidal vasculopathy (PCV). Furthermore, we investigated associations of age, lesion size, and single nucleotide polymorphisms (SNPs) in CFH and ARMS2 genes with treatment response. Results: Forty-nine eyes were diagnosed with typical neovascular AMD and 56 eyes with PCV. Serous retinal detachment and retinal edema resolved similarly in both typical neovascular AMD and PCV after treatment. However, visual acuity (VA) significantly improved in eyes with PCV, whereas VA was maintained in typical neovascular AMD. At the third and twelfth months after injection, VA was better in PCV than in typical neovascular AMD (P = .027 and P = .044, respectively), although there were no differences in baseline VA between the 2 groups. Age and size of greatest linear dimension were significantly associated with visual prognosis in typical neovascular AMD but not in PCV. There was no clear association between 3 SNPs and responsiveness to ranibizumab treatment. Conclusions: Although exudative changes were equivalent following ranibizumab treatment in both typical neovascular AMD and PCV, there was a significant increase in VA in PCV compared to typical neovascular AMD. Age and greatest linear dimension correlated with visual prognosis only in typical neovascular AMD and not in PCV.

Sleep Apnea and Risk of Retinal Vein Occlusion: A Nationwide Population-Based Study of Taiwanese - Corrected Proof

2012-04-01

Purpose: To explore the relationship of sleep apnea and the subsequent development of retinal vein occlusion (RVO). Design: A retrospective nonrandomized, matched-control cohort study using the Taiwan National Health Insurance Research Database. Methods: From 1997 through 2007, we identified newly diagnosed sleep apnea cases in the database. A control group without sleep apnea, matched for age, gender, and comorbidities, was selected for comparison. The 2 cohorts were followed up, and the occurrence of RVO was observed. Results: Of the 35 634 sampled patients (5965 sleep apnea patients vs 29 669 controls), 52 (0.15%) experienced RVO during a mean follow-up period of 3.72 years, including 13 (0.22%, all branch RVO) from the sleep apnea cohort and 39 (0.13%, 39 branch RVO and 10 central RVO) from the control group. Kaplan-Meier analysis revealed the tendency of sleep apnea patients toward RVO development (P = .048, log-rank test). Patients with sleep apnea experienced a 1.94-fold increase (95% confidence interval, 1.03 to 3.65; P = .041) in incident RVO, which was independent of age, gender, and comorbidities. Conclusions: Sleep apnea may be an independent risk factor for RVO.

Comparison of Through-Focus Image Sharpness Across Five Presbyopia-Correcting Intraocular Lenses - Corrected Proof

Jay S. Pepose, Daozhi Wang, Griffith E. Altmann — 2012-04-01

Purpose: To assess through-focus polychromatic image sharpness of 5 FDA-approved presbyopia-correcting intraocular lenses (IOLs) through a range of object vergences and pupil diameters using an image sharpness algorithm. Design: Laboratory investigation. Methods: A 1951 USAF resolution target was imaged through Crystalens AO (AO), Crystalens HD (HD), aspheric ReSTOR +4 (R4), aspheric ReSTOR +3 (R3), and Tecnis Multifocal Acrylic (TMF) IOL in a model eye and captured digitally for each combination of pupil diameter and object vergence. The sharpness of each digital image was objectively scored using a 2-dimensional gradient function. Results: AO had the best distance image sharpness for all pupil diameters and was superior to the HD. With a 5-mm pupil, the R4 distance image sharpness was similar to the HD and at 6 mm the TMF was superior to the HD, R3, and R4. The R3 moved the near focal point farther from the patient compared to the R4, but did not improve image sharpness at intermediate distances and showed worse distance and near image sharpness. Consistent with apodization, the ReSTOR IOLs displayed better distance and poorer near image sharpness as pupil diameter increased. TMF showed consistent distance and near image sharpness across pupil diameters and the best near image sharpness for all pupil diameters. Conclusions: Differing IOL design strategies to increase depth of field are associated with quantifiable differences in image sharpness at varying vergences and pupil sizes. Objective comparison of the imaging properties of specific presbyopia-correcting IOLs in relation to patient's pupil sizes can be useful in selecting the most appropriate IOL for each patient.

Determinants of Lens Vault and Association With Narrow Angles in Patients From Singapore - Corrected Proof

2012-04-01

Purpose: To describe the distribution and determinants of lens vault and to investigate the association of lens vault with narrow angles. Design: Prospective cross-sectional study. Methods: Phakic subjects 50 years and older were evaluated at a primary healthcare clinic with gonioscopy, partial laser interferometry, and anterior segment optical coherence tomography (AS-OCT). Narrow angles were defined as posterior trabecular meshwork not visible for ≥2 quadrants on non-indentation gonioscopy. Lens vault was defined as the perpendicular distance between the anterior pole of the crystalline lens and the horizontal line joining the 2 scleral spurs on horizontal AS-OCT scans. Analysis of covariance, multivariate logistic regression, and area under the receiver operating characteristic curves (AUC) were performed. Results: Of the 2047 subjects recruited, 582 were excluded because of poor image quality or inability to locate scleral spurs, leaving 1465 subjects for analysis. Eyes with narrow angles had greater lens vault compared to eyes with open angles (775.6 µm vs 386.5 µm, P < .0001). Women had significantly greater lens vault than men (497.28 µm vs 438.56 µm, P < .001), and lens vault increased significantly with age (P for trend 667.6 µm were more likely to have narrow angles (OR 2.201, 95% CI: 1.070-4.526) compared to those with lens vault ≤462.7 µm. The AUC for lens vault (0.816) and ACD (0.822) for detecting narrow angles were similar (P = .582). Conclusions: Lens vault was independently associated with narrow angles and may be useful in screening to detect eyes with narrow angles.

Immunologic and Genetic Markers in Patients With Idiopathic Ocular Inflammation and a Family History of Inflammatory Bowel Disease - Corrected Proof

2012-04-01

Purpose: To evaluate the prevalence of immunologic and genetic markers in patients with idiopathic ocular inflammation and a family history of inflammatory bowel disease. Design: Matched case-control study. Methods: Patients with a diagnosis of idiopathic ocular inflammation and family history of inflammatory bowel disease who did not have inflammatory bowel disease themselves were identified and matched to control patients with idiopathic ocular inflammation. Serum was evaluated for immunologic markers using Prometheus IBD Serology 7. Genomic DNA was analyzed for single nucleotide polymorphisms (SNP) of the NOD2 gene associated with Crohn disease. Results: Fifteen patients with idiopathic ocular inflammation and family history of inflammatory bowel disease were matched to 15 control patients based on age, sex, and race. Eight of 15 patients (53%) with a family history of inflammatory bowel disease had elevated p-ANCA antibody levels compared to 3 of 15 controls (20%) (1-sided P = .04) with a matched analysis odds ratio of 6.0 (1-sided P = .06). Four of 15 patients (27%) with family history of inflammatory bowel disease tested positive for immunologic markers predicting ulcerative colitis, while no control patients tested positive (1-sided P = .06). Carrier rates of NOD2 SNPs did not differ significantly between the test and control groups. Conclusions: One-quarter of patients with idiopathic ocular inflammation and a family history of inflammatory bowel disease had immunologic markers predicting bowel disease, and one-half had elevated p-ANCA levels. Prometheus IBD Serology 7 may be useful in the evaluation of selected patients with unexplained uveitis.

Progression of Retinal Pigment Epithelial Atrophy in Stargardt Disease - Corrected Proof

Vikki A. McBain, John Townend, Noemi Lois — 2012-04-01

Purpose: To evaluate retinal pigment epithelial (RPE) atrophy in patients with Stargardt disease using autofluorescence imaging (AF). Design: Retrospective observational case series. Methods: Demographics, best-corrected visual acuity (BCVA), AF images, and electrophysiology responses (group 1, macular dysfunction; group 2, macula + cone dysfunction; group 3, macula + cone-rod dysfunction) were evaluated at presentation and follow-up in a group of 12 patients (24 eyes) with Stargardt disease. The existence, development, and rate of enlargement of areas of RPE atrophy over time were evaluated using AF imaging. A linear regression model was used to investigate the effects of AF and electrophysiology on rate of atrophy enlargement and BCVA, adjusting for age of onset and duration of disease. Results: Eight male and 4 female patients (median age 42 years; range 24−69 years) were followed for a median of 41.5 months (range 13−66 months). All 12 patients had reduced AF compatible with RPE atrophy at presentation and in all patients the atrophy enlarged during follow-up. The mean rate of atrophy enlargement for all patients was 1.58 mm2/y (SD 1.25 mm2/y; range 0.13−5.27 mm2/y). Only the pattern of functional loss present as detected by electrophysiology was statistically significantly associated with the rate of atrophy enlargement when correcting for other variables (P < .001), with patients in group 3 (macula + cone-rod dysfunction) having the fastest rate of atrophy enlargement (1.97 mm2/y, SD 0.70 mm2/y) (group 1 [macula] 1.09 mm2/y, SD 0.53 mm2/y; group 2 [macula + cone] 1.89 mm2/y, SD 2.27 mm2/y). Conclusion: Variable rates of atrophy enlargement were observed in patients with Stargardt disease. The pattern of functional loss detected on electrophysiology was strongly associated with the rate of atrophy enlargement over time, thus serving as the best prognostic indicator for patients with this inherited retinal disease.

Descemet Membrane Endothelial Keratoplasty Combined With Phacoemulsification and Intraocular Lens Implantation: Advanced Triple Procedure - Corrected Proof

2012-04-01

Purpose: To evaluate the functional and morphologic outcome of Descemet membrane endothelial keratoplasty (DMEK) combined with phacoemulsification and intraocular lens implantation in patients suffering from endothelial dysfunction and cataract. Design: Retrospective, single-center, consecutive case series. Methods: Triple-DMEK (DMEK with simultaneous cataract surgery) was performed in 61 consecutive eyes of 56 patients using corneal donor tissue pre-stored in either short-term culture (Optisol-GS) at 4 C or organ culture (Dulbecco's modified Eagle's medium, CorneaMax medium) at 34 C. Main outcome measures included the number of air injections necessary for graft attachment as well as best-corrected visual acuity (BCVA [logMAR]), central corneal thickness (CCT), endothelial cell density (ECD), refractive spherical equivalent, refractive cylinder, and topographic cylinder at 1, 3, and 6 months postoperatively. Results: BCVA increased from 0.6 ± 0.23 logMAR preoperatively (n = 54) to 0.19 ± 0.22 logMAR at 6 months (n = 27) after surgery (P ≤ .05). ECD of donor corneas decreased from 2573 ± 235 cells/mm2 (n = 61) to 1550 ± 326 cells/mm2 (n = 29) after 6 months (P ≤ .05). CCT decreased from 651 ± 69 μm (n = 54) preoperatively to 521 ± 65 μm (n = 27) after 6 months (P ≤ .05). Refractive spherical equivalent was −0.3 ± 2.8 D (n = 27) preoperatively and 0.9 ± 1.5 D 6 months (n = 27) after surgery. A total of 54.5% of eyes were within 1 D of emmetropia (n = 12) and 77.3% were within 2 D of emmetropia (n = 17) 6 months (n = 22) after surgery. Refractive cylinder was −0.9 ± 1.0 D preoperatively (n = 49) and −1.5 ± 1.0 D 6 months (n = 23) after surgery. The change in refractive cylinder within the first month was statistically significant (P ≤ .05; Wilcoxon test). Topographic cylinder was 2.1 ± 1.7 D preoperatively (n = 58) and 1.7 ± 1.1 D 6 months (n = 28) after surgery. Between 3 and 6 months a significant change in topographic cylinder towards lower values was measured (P ≤ 0.05; Wilcoxon test). Optimized spherical results were achieved by selecting intraocular lenses based on a hyperopic shift of −0.75 D. Conclusion: DMEK combined with cataract surgery (triple procedure) can routinely be performed in cases of endothelial dystrophy and cataract. The addition of cataract surgery to DMEK had no adverse effect on endothelial function or graft adhesion and did not increase the likelihood of postoperative complications.

Franceschetti Hereditary Recurrent Corneal Erosion - Corrected Proof

2012-03-09

Purpose: To describe new affected individuals of Franceschetti's original pedigree of hereditary recurrent erosion and to classify a unique entity called Franceschetti corneal dystrophy. Design: Observational case series. Methods: Slit-lamp examination of 10 affected individuals was conducted. Biomicroscopic examinations were supplemented by peripheral corneal biopsy in 1 affected patient with corneal haze. Tissue was processed for light and electron microscopy and immunohistochemistry was performed. DNA analysis was carried out in 12 affected and 3 nonaffected family members. Results: All affected individuals suffered from severe ocular pain in the first decade of life, attributable to recurrent corneal erosions. Six adult patients developed bilateral diffuse subepithelial opacifications in the central and paracentral cornea. The remaining 4 affected individuals had clear corneas in the pain-free stage of the disorder. Histologic and immunohistochemical examination of the peripheral cornea in a single patient showed a subepithelial, avascular pannus. There was negative staining with Congo red. DNA analysis excluded mutations in the transforming growth factor beta–induced (TGFBI) gene and in the tumor-associated calcium signal transducer 2 (TACSTD2) gene. Conclusion: We have extended the pedigree of Franceschetti corneal dystrophy and elaborated its natural history on the basis of clinical examinations. A distinctive feature is the appearance of subepithelial opacities in adult life, accompanied by a decreased frequency of recurrent erosion attacks. Its clinical features appear to distinguish it from most other forms of dominantly inherited recurrent corneal erosion reported in the literature.

Descemet Membrane Endothelial Keratoplasty Versus Descemet Stripping Automated Endothelial Keratoplasty - Corrected Proof

2012-03-07

Purpose: To evaluate visual outcome and endothelial cell survival after Descemet membrane endothelial keratoplasty (DMEK) in comparison with Descemet stripping automated endothelial keratoplasty (DSAEK). Design: Single-center, retrospective, consecutive case series. Methods: Thirty-eight eyes of 38 consecutive patients undergoing DMEK, who completed a 6-month follow-up, were compared with 35 eyes of 35 consecutive patients undergoing DSAEK for Fuchs endothelial dystrophy or pseudophakic bullous keratopathy. Main outcome measures included best-corrected visual acuity (in logarithm of the minimal angle of resolution [logMAR] units) and endothelial cell density within a 6-month follow-up. Results: Best-corrected visual acuity increased from 0.70 ± 0.48 logMAR and 0.75 ± 0.32 logMAR before surgery to 0.21 ± 0.14 logMAR and 0.48 ± 0.19 logMAR 3 months after DMEK and DSAEK (P < .001), respectively, and to 0.17 ± 0.12 logMAR and 0.36 ± 0.15 logMAR 6 months after DMEK and DSAEK (P < .001), respectively. Endothelial cell density decreased from 2575 ± 260 cells/mm2 and 2502 ± 220 cells/mm2 before surgery to 1498 ± 244 cells/mm2 and 1778 ± 420 cells/mm2 3 months after DMEK and DSAEK (P < .001), respectively, and to 1520 ± 299 cells/mm2 and 1532 ± 495 cells/mm2 6 months after DMEK and DSAEK (P = .483), respectively. Central corneal thickness decreased from 652 ± 92 μm before surgery to 517 ± 45 μm 6 months after DMEK, and from 698 ± 137 μm before surgery to 618 ± 66 μm 6 months after DSAEK. Conclusions: DMEK provided faster and more complete visual rehabilitation when compared with DSAEK. However, there were no significant differences concerning endothelial cell survival within a 6-month follow-up.

Macular Choroidal Thickness and Volume in Eyes With Angioid Streaks Measured by Swept Source Optical Coherence Tomography - Corrected Proof

2012-03-07

Purpose: To study the mean choroidal thickness and volume of the macula in eyes with angioid streaks using swept source optical coherence tomography (OCT) in the 1050-nm wavelength range. Design: Prospective case series. Methods: The macular area of 39 eyes of 23 patients with angioid streaks and of 20 normal eyes of 20 matched controls (Group 1) was studied with a swept source OCT prototype system. Eyes with angioid streaks were classified into 1 of 4 groups: those without choroidal neovascularization (CNV) (Group 2); those with CNV that had no history of treatment (Group 3); those with CNV that had previously received only anti–vascular endothelial growth factor treatments (Group 4); and those with CNV that had previously received photodynamic therapy (Group 5). Using a raster scan protocol with 512 × 128 A-scans, we produced a macular choroidal thickness map (6 × 6 mm2). Results: There were no significant differences in age, axial length, or refractive error among the 5 groups. Mean choroidal thickness of the macula in Group 2 (218.9 ± 46.8 μm) was as great as that in Group 1 (218.8 ± 69.2 μm). However, the macular choroidal thickness in Group 3 (119.7 ± 49.2 μm), Group 4 (140.1 ± 64.9 μm), and Group 5 (144.0 ± 52.6 μm) was significantly less than that of Group 1 (P < .05). There were no statistical differences between Groups 3 through 5. In each group, the choroid of the nasal quadrant was significantly thinner compared to that in other quadrants (P < .05). Conclusions: The choroid in eyes with angioid streaks without CNV was as thick as that in normal controls, but was significantly thinner in eyes with angioid streaks that had developed CNV.

Outcomes of Trabeculectomy After Descemet Stripping Automated Endothelial Keratoplasty: A Comparison With Penetrating Keratoplasty - Corrected Proof

Pui Yi Boey, Jodhbir S. Mehta, Ching Lin Ho, Donald T.H. Tan, Tina T. Wong — 2012-03-07

Purpose: To compare the outcomes of trabeculectomy surgery after Descemet stripping automated endothelial keratoplasty (DSAEK) to penetrating keratoplasty (PK). Design: Retrospective case-control study. Methods: Patients within an institutional setting who underwent trabeculectomy with mitomycin C (MMC) for uncontrolled elevated intraocular pressure (IOP) after corneal graft surgery were included. Patients with pre-existing glaucoma were excluded. Twenty patients with trabeculectomy after DSAEK and 41 patients with trabeculectomy after PK were analyzed. The main outcome measure was IOP control at 12 months. Secondary outcome measures were postoperative interventions including reinstatement of IOP-lowering medications, bleb needling with 5-fluorouracil (5FU) or further glaucoma surgery, and the incidence of complications related to trabeculectomy and/or corneal graft surgery. Results: There was no difference in pre-trabeculectomy IOP between DSAEK vs PK group (35.5 ± 10.1 vs 32.9 ± 8.9, P = .31). At 12 months after trabeculectomy, mean IOP in the DSAEK group was lower compared to the PK controls (10.6 ± 3.2 vs 14.6 ± 8.5, P = .04). The proportion of patients who achieved an IOP less than 12 mm Hg was significantly higher in the DSAEK group (80.0% vs 48.6%, P = .03). The proportions of eyes that required intervention after trabeculectomy were comparable between the 2 groups (DSAEK vs PK, all interventions: 20.0% vs 39.5%, P = .15; IOP-lowering medications required: 15.0% vs 39.5%, P = .08; needling with 5FU: 20.0% vs 23.7%, P > .99; further glaucoma surgery: 0% vs 13.2%, P = .15). Corneal graft failure arising after trabeculectomy was seen in 10.0% of DSAEK cases and in 10.5% of PK controls (P = 1.0). Conclusion: Compared to trabeculectomy after PK, trabeculectomy after DSAEK achieved lower mean IOP at 12 months, and a larger proportion of DSAEK patients achieved an IOP of less than 12 mm Hg. There was no difference in the need for intervention after trabeculectomy, or incidence of other complications. Trabeculectomy is an effective surgical procedure for the management of postgraft ocular hypertension in DSAEK patients, and DSAEK may have an advantage in terms of success of trabeculectomy surgery over PK.

Real-time Polymerase Chain Reaction in the Diagnosis of Acute Postoperative Endophthalmitis - Corrected Proof

2012-03-01

Purpose: To evaluate the efficacy of quantitative real-time polymerase chain reaction (qPCR) in the diagnosis of postoperative bacterial endophthalmitis among patients who underwent cataract surgery at a tertiary care center. Design: Prospective experimental study. Methods: This was a single-center study of 64 eyes of 64 patients presenting with clinical signs and symptoms of endophthalmitis within 1 year of cataract surgery. Patients with glaucoma filtering or cornea surgery in the past year, postoperative trauma, fungal endophthalmitis, or preoperative inflammatory conditions were excluded. Vitreous samples were obtained during vitreous tap or vitrectomy and sent for both culture and qPCR with sequencing. Vitreous samples obtained from 50 patients undergoing vitrectomy for noninflammatory indications served as controls. The main outcome measures were the sensitivity of qPCR compared to culture and concordance of results of pathogen identification with sequencing vs phenotypic speciation. Results: qPCR detected 16s bacterial DNA in 37 patients (66%), compared to 19 (34%) with traditional culture. Only 1 patient had a positive result by culture (Nocardia species) but negative result by qPCR. For the 18 samples positive by both qPCR and culture, there was a 100% concordance in pathogen identification between sequencing and phenotypic speciation. Conclusion: In cases of suspected bacterial endophthalmitis, qPCR offers an improved diagnostic yield and may be a useful adjunct to traditional culture. Further large-scale clinical studies are needed to elucidate the full clinical utility of qPCR.

The Short-term Effects of Antioxidant and Zinc Supplements on Oxidative Stress Biomarker Levels in Plasma: A Pilot Investigation - Corrected Proof

2012-03-01

Purpose: To determine if short-term Age-Related Eye Disease Study (AREDS) antioxidant and zinc supplementation affects biomarkers of oxidative stress, possibly serving as a predictor of their efficacy. Design: Prospective interventional case series. Methods: Nineteen subjects, 12 with intermediate or advanced age-related macular degeneration (AMD) (AREDS categories 3 or 4) and 7 non-AMD controls, were admitted to the Vanderbilt General Clinical Research Center and placed on a controlled diet for 7 days. Antioxidant and zinc supplements were stopped 2 weeks prior to study enrollment. Dietary supplementation with 500 mg vitamin C, 400 IU vitamin E, 15 mg β-carotene, 80 mg zinc oxide, and 2 mg cupric oxide per day was instituted on study day 2. Blood was drawn on study days 2 and 7, and plasma concentrations of cysteine (Cys), cystine (CySS), glutathione (GSH), isoprostane (IsoP), and isofuran (IsoF) were determined. Results: Short-term AREDS supplementation significantly lowered mean plasma levels of CySS in participants on a regulated diet (P = .034). No significant differences were observed for Cys, GSH, IsoP, or IsoF. There were no significant differences between AMD patients and controls. Conclusions: This pilot interventional study shows that a 5-day course of antioxidant and zinc supplements can modify plasma levels of CySS, suggesting that this oxidative stress biomarker could help predict how likely an individual is to benefit from AREDS supplementation. Further, CySS may be useful for the evaluation of new AMD therapies, particularly those hypothesized to affect redox status.

Cataract Surgery in Eyes With Nanophthalmos and Relative Anterior Microphthalmos - Corrected Proof

Kyoung In Jung, Ji Wook Yang, Young Chun Lee, Su-Young Kim — 2012-02-27

Purpose: To compare the refractive outcome and postoperative complications of cataract surgery among nanophthalmos and relative anterior microphthalmos and the normal control eyes. Design: Retrospective case-control series. Methods: Seventeen eyes with nanophthalmos, 29 eyes with relative anterior microphthalmos, and 54 normal control eyes were enrolled in this study. The subjects were divided into 3 diagnostic subgroups according to the following: nanophthalmos with an axial length <20.5 mm and without morphologic malformation; relative anterior microphthalmos with a corneal diameter (CD) ≤11 mm, an anterior chamber depth (ACD) ≤2.2 mm, and an axial length (AL) ≥ 20.5 mm; and normal control group eyes defined as an AL ≥20.5 mm with a CD >11 mm or an ACD >2.2 mm. The implanted intraocular lens (IOL) power was used to calculate the predicted postoperative refraction error according to 4 IOL power formulas: SRK II, SRK/T, Hoffer Q, and Holladay 1. With each formula, the mean numeric error and mean absolute error were calculated. At postoperative 2 months, the endothelial cell count and the complications were analyzed. Results: As measured by mean numeric error or mean absolute error, there was a significant difference among the 3 groups based on SRK II, SRK/T, and Hoffer Q, with less predictability in the nanophthalmic eyes. In eyes with nanophthalmos, the Holladay 1 produced the best refractive results as measured by mean numeric error (P < .001). A higher occurrence rate of posterior capsule rupture (11.7%) was shown in the nanophthalmic eyes. The difference among the 3 groups for the postoperative endothelial cell loss was not significant (P = .421). Conclusions: The refractive predictability and postoperative outcome was poorer in the eyes with nanophthalmos compared to the eyes with relative anterior microphthalmos or normal control.

Visual Performance After Posterior Chamber Phakic Intraocular Lens Implantation and Wavefront-Guided Laser In Situ Keratomileusis for Low to Moderate Myopia - Corrected Proof

2012-02-24

Purpose: To compare postoperative visual function after implantable collamer lens (ICL) implantation and after wavefront-guided laser in situ keratomileusis (LASIK) in eyes with low to moderate myopia. Design: Retrospective observational case study. Patients and Methods: We investigated 30 eyes of 20 patients undergoing ICL implantation and 64 eyes of 38 patients undergoing wavefront-guided LASIK for the correction of low to moderate myopia (manifest spherical equivalent: −3.00 to −5.88 diopters [D]). Ocular higher-order aberrations (HOAs) and contrast sensitivity (CS) function were measured by Hartmann-Shack aberrometry and a contrast sensitivity unit before and 3 months after surgery, respectively. From the contrast sensitivity, the area under the log contrast sensitivity function was calculated. Results: For 4-mm and 6-mm pupils, the changes in ocular third-order aberrations, fourth-order aberrations, and total HOAs after ICL implantation were significantly less than those after wavefront-guided LASIK (P < .05, Mann-Whitney U test). The postoperative area under the log contrast sensitivity function was significantly increased after ICL implantation (P < .001), whereas, after wavefront-guided LASIK, it was not significantly changed (P = .11). Conclusions: ICL implantation induces significantly fewer ocular HOAs than wavefront-guided LASIK. Moreover, CS was significantly improved after ICL implantation but unchanged after wavefront-guided LASIK in eyes with low to moderate myopia. Thus, even in the correction of low to moderate myopia, ICL implantation appears to be superior in visual performance to wavefront-guided LASIK, suggesting that it may be a viable surgical option for the treatment of such eyes.

Accuracy of Intraocular Lens Power Calculation Formulae in Children Less Than Two Years - Corrected Proof

2012-02-15

Purpose: To assess the accuracy of IOL power calculation formulae in children less than 2 years of age. Design: Retrospective, comparative study, comprising of 128 eyes of 84 children. Methods: We analyzed records of children less than 2 years with congenital cataract who underwent primary IOL implantation. Data were analyzed for prediction error using the 4 commonly used IOL power calculation formulae. We calculated the absolute prediction error with each of the formulae and the formula that gave least variability was determined. The formula that gave the best prediction error was determined. Results: Mean age at surgery was 11.7 ± 6.2 months. Absolute prediction error was found to be 2.27 ± 1.69 diopters (D) with SRK II, 3.23 ± 2.24 D with SRK T, 3.62 ± 2.42 D with Holladay, and 4.61 ± 3.12 D with Hoffer Q. The number of eyes with absolute prediction error within 0.5 D was 27 (21.1%) with SRK II, 8 (6.3%) with SRK T, 12 (9.4%) with Holladay, and 5 (3.9%) with Hoffer Q. Comparison between different formulae showed that the absolute prediction error with SRK II formula was significantly better than with other formulae (P < .001). Prediction error with SRK II formula was not affected by any factor such as age (P = .31), keratometry (P = .32), and axial length (P = .27) of the patient. Axial length influenced the absolute prediction error with Holladay (P = .05) and Hoffer Q formulae (P = .002). Mean keratometry influenced prediction error (P = .03) with SRK T formula. Conclusion: Although absolute prediction error tends to remain high with all present IOL power calculation formulae, SRK II was the most predictable formula in our series.

A Phase 2 Randomized, Double-Masked, Placebo-Controlled Study of a Novel Integrin Antagonist (SAR 1118) for the Treatment of Dry Eye - Corrected Proof

2012-02-13

Purpose: To investigate the efficacy and safety of an investigational integrin antagonist (SAR 1118) ophthalmic solution compared to placebo (vehicle) in subjects with dry eye disease. Design: Multicenter, prospective, double-masked, placebo-controlled trial. Methods: A total of 230 dry eye subjects selected with use of a controlled adverse environment were randomized 1:1:1:1 to receive SAR 1118 (0.1%, 1.0%, 5.0%) or placebo eye drops twice daily for 84 days. Principal eligibility criteria included exacerbation in corneal staining and ocular symptoms with controlled adverse environment exposure, no active lid margin disease, and Schirmer test (mm/5 min) >1 and <10. Ocular signs and symptoms (Ocular Surface Disease Index, OSDI) were assessed at day 14, 42, and 84. No supplemental artificial tears were allowed. Primary outcome measure was inferior corneal staining score at day 84. Results: A dose response for the corneal staining score (P = .0566) was observed for SAR 1118 at day 84 compared to placebo. Mean change from baseline to day 84 showed significant improvements (P < .05) in corneal staining score, total OSDI, and visual-related function OSDI scores for SAR 1118 compared to placebo; improvements in tear production and symptoms were observed as early as day 14 (P < .05). Adverse events were mild and transient in nature with no serious ocular adverse events. SAR 1118 5.0% showed increased instillation site adverse events relative to placebo but were limited to the initial dose. Conclusion: SAR 1118 demonstrated improvements in signs and symptoms of dry eye compared to placebo and appears safe when administered over 84 days.

Calcification in Hydrophilic Intraocular Lenses Associated With Injection of Intraocular Gas - Corrected Proof

Anish Dhital, David J. Spalton, Saurabh Goyal, Liliana Werner — 2012-02-13

Purpose: To report a distinct type of calcification in hydrophilic intraocular lenses in complicated, traumatized eyes with a history of intraocular gas use. Design: Observational case series. Methods: Three cases of hydrophilic intraocular lens (IOL) opacification confined to the pupillary area are reported from clinical practice in London, UK. Clinical details and analysis of the explanted intraocular lenses are provided with environmental scanning electron microscopy images and x-ray energy-dispersive spectroscopy results. Results: All cases were associated with use of intraocular gas in complicated traumatized eyes, and had central areas of IOL opacification over the pupillary zone, confined to the anterior surface of the IOL. Analysis of the lenses showed the opacified areas to be composed of calcium and phosphate. Conclusion: The areas of opacification in all 3 hydrophilic IOLs were attributable to calcification. We postulate that intraocular gas use and the altered blood-aqueous barrier of these complicated traumatized eyes co-act to trigger secondary IOL calcification. Further experimental testing is needed to confirm this clinical association.

Wavefront-Guided and Aspheric Ablation for Myopia – One-Year Results of the Zyoptix Personalized Treatment Advanced Algorithm - Corrected Proof

Andrea Ryan, Michael O'Keefe — 2012-02-13

Purpose: To evaluate the visual outcome and change in higher-order aberrations (HOAs) 1 year post simultaneous wavefront-guided and aspheric photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). Design: Prospective interventional case series. Methods: Consecutive myopic patients undergoing PRK (38 eyes of 23 patients) and LASIK (42 eyes of 25 patients) using the Technolas 217z100 excimer laser (Technolas Perfect Vision) in a private laser clinic were included. Main outcome measures were uncorrected distance visual acuity (UDVA), manifest refraction (MRSE), HOAs, and spherical aberration (Z40). Results: At 1 year, 87% (32/37) of PRK eyes and 81% (30/37) of LASIK eyes had UDVA of 20/20 or better (P = .75). Mean ± SD MRSE was −0.26 ± 0.31 diopters (D) in the PRK and −0.16 ± 0.34 D in the LASIK group (P = .222). There was no significant increase in total HOA root mean square (RMS) in the PRK group. Mean ± SD total HOA RMS increased from 0.402 ± 0.14 μm to 0.496 ± 0.17 μm (P = .013) in the LASIK group at 1 year. Z40 increased from mean ± SD −0.045 ± 0.12 μm to −0.109 ± 0.15 μm (P = .006, factor 2.42) in the PRK group and did not significantly increase in the LASIK group (mean ± SD −0.16 ± 0.17 μm to −0.17 ± 0.15 μm (P = .469, factor 1.08) at 6 mm pupil. Conclusions: Visual outcome was excellent in both treatment groups. HOAs were still increased following LASIK by a factor of 1.23 but not PRK. Z40 was not induced by LASIK with the treatment algorithm but was negatively induced in PRK eyes.

Impact of Ocular Surface Symptoms on Quality of Life in a United States Veterans Affairs Population - Corrected Proof

2012-02-13

Purpose: To evaluate the impact of ocular surface symptoms on quality of life in a veteran population receiving eye care services. Design: Cross-sectional survey study. Methods: Setting: Miami Veterans Affairs Medical Center (VAMC). Patient population: Patients seen at the eye clinic between June and August 2010 were asked to fill out the Dry Eye Questionnaire 5 (DEQ5) and the Impact of Dry Eye on Everyday Life (IDEEL) questionnaire. MAIN OUTCOME MEASURES: Correlation between ocular surface symptoms and functionality. Results: Four hundred eighty-nine patients elected to fill out the DEQ5 questionnaire (36% response rate). The mean age of respondents was 66 years (standard deviation 12). Ninety-four percent were male; 62% were white and 37% were black. Using the DEQ5 as a surrogate measure of ocular surface symptoms, 65% of respondents reported at least mild ocular surface symptoms (DEQ5 ≥6) and 27% of them reported severe symptoms (DEQ5 ≥12). Black subjects had a 2-fold increased risk of severe symptoms compared to white subjects (odds ratio 2.06, 95% confidence interval 1.33-3.19). Several medications were associated with a significantly increased risk of severe symptoms, including glaucoma medications (1.7-fold increase), antidepressants (2.3-fold increase), and antihistamines (2.1-fold increase). There was an inverse correlation between DEQ5 and IDEEL scores with regard to ability to perform activities of daily living (n = 391, r = −0.54, P < .001), emotional well-being (n = 386, r = −0.63, P < .001), and the ability to work (n = 205, r = −0.57, P < .001). Fifty percent of patients with severe symptoms had documentation that their symptoms were addressed during the visit. Conclusion: Severe ocular surface symptoms reduce the quality of life of Miami VAMC veterans. Eye care professionals should be vigilant in eliciting ocular surface complaints from their patients.

Microperimetric Correlations of Autofluorescence and Optical Coherence Tomography Imaging in Dry Age-Related Macular Degeneration - Corrected Proof

Lea Querques, Giuseppe Querques, Raimondo Forte, Eric H. Souied — 2012-02-09

Purpose: To investigate the microperimetric correlations of autofluorescence imaging and optical coherence tomography (OCT) in dry age-related macular degeneration (AMD). Design: Retrospective, observational, cross-sectional study. Methods: Consecutive patients with dry AMD underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA), blue fundus autofluorescence (FAF), near-infrared autofluorescence, and spectral-domain (SD)-OCT with integrated microperimetry. Results: A total of 58 eyes of 29 patients (21 women; mean age 73 ± 9 years) were included. Mean BCVA was 0.28 ± 0.3 logarithm of the minimal angle of resolution (logMAR). Overall, 2842 points were analyzed as regards FAF and near-infrared autofluorescence patterns, the status of inner segment/outer segment (IS/OS) interface, and retinal sensitivity. We observed a good correlation between the FAF and near-infrared autofluorescence patterns for all the points graded (increased FAF/near-infrared autofluorescence, Pearson rho = 0.6, P = .02; decreased FAF/near-infrared autofluorescence, Pearson rho = 0.7, P = .01; normal FAF/near-infrared autofluorescence, Pearson rho = 0.7, P = .01). Mean retinal sensitivity was significantly reduced in cases of decreased FAF (4.73 ± 2.23 dB) or increased FAF (4.75 ± 2.39 dB) compared with normal FAF (7.44 ± 2.34 dB) (P = .001). Mean retinal sensitivity was significantly reduced in case of decreased near-infrared autofluorescence (3.87 ± 2.28 dB), compared with increased near-infrared autofluorescence (5.76 ± 2.44 dB) (P = .02); mean retinal sensitivity in case of increased near-infrared autofluorescence was significantly reduced compared with normal near-infrared autofluorescence (7.15 ± 2.38 dB) (P = .002). On SD-OCT, there was a high inverse correlation between retinal sensitivity and rate of disruptions in IS/OS interface (Pearson rho = −0.72, P = .001). Conclusion: A reduced retinal sensitivity consistently correlates with decreased FAF/near-infrared autofluorescence and a disrupted IS/OS interface. Increased near-infrared autofluorescence may represent a useful method for detection of retinal abnormalities early in dry AMD development.