Abstract: Purpose: The present study aimed at determining differences in riboflavin concentration in the anterior, intermediate and posterior stroma after three corneal cross-linking imbibition techniques (standard Epi-off, Epi-on and Iontophoresis-assisted administration) of 0.1% riboflavin.Design: Experimental laboratory investigation of human cadaver corneas not suitable for transplantation.Methods: 10 corneas underwent imbibition with Epi-on (n=3), Epi-off (n=3), iontophoresis (n=3) and saline exposure (control; n=1). Femtosecond laser was used to produce three 8mm discs of the superficial (0-150μm), intermediate (150-300μm) and deep stroma (>300μm). Riboflavin concentration was measured with High-Performance Liquid Chromatography. The main outcome measure was riboflavin concentration at the three evaluated depths.Results: The overall stromal concentration of riboflavin was 34.1±7.1 μg/g in Epi-off, 7.2±3.7 μg/g in Epi-on and 15.0±5.1 μg/g in Iontophoresis. The mean riboflavin content in the superficial slice in the Epi-off group was about two-fold greater than that of the Iontophoresis group (50.5±5.3 μg/g and 23.6±2.5 μg/g, respectively) and four-fold greater than that of the Epi-on group (11.7±3.3 μg/g). Similar differences among the three groups were observed for the intermediate and posterior stromal slices, presenting an evident reduction of riboflavin concentration with increasing depth in all groups. Slice depth-dependent decrease in riboflavin concentration was statistically significant (General Linear Model (GLM); F1,6=62.265, p<0.001), as was the group-dependent variation (GLM; F2,6=20.268, p=0.002) and the slice depth-group interaction (GLM; F2,6=18.004, p=0.002).Conclusions: Corneal cross-linking transepithelial ionotphoresis imbibition yielded greater and deeper riboflavin saturation with respect to conventional Epi-on, while maintaining the advantages of avoiding epithelial removal and shorter procedure-time, but did not reach concentrations obtained with standard Epi-off.
Category: Peer-reviewed
DNA Mismatch Repair Defects and Microsatellite Instability Status in Periocular Sebaceous Carcinoma – Accepted Manuscript
Abstract: Purpose: To characterize mismatch repair protein expression and the role of DNA repair abnormalities in sebaceous carcinomas of the ocular adnexa.Design: This was a retrospective, case series studyMethods: We reviewed ten cases of sporadic se…
Clinic-Based Glaucoma Care in the Era of Surgical Subspecialization – Accepted Manuscript
Abstract: Purpose: To evaluate the impact of surgeon practice profile on clinic-based glaucoma care.Design: Population-based study of glaucoma care patterns in Ontario, Canada from 2000 to 2010.Methods: Using comprehensive physician services data from the Ontario Health Insurance Plan database, ophthalmologists were divided into five surgical practice subgroups. The role of each subgroup in the provision of glaucoma care was evaluated. Consultations and office visits were used to assess non-surgical care, while laser trabeculoplasty procedures were used to assess clinic-based procedural care.Results: Between 2000 and 2010, the population rate of glaucoma consultations and follow up visits provided by ophthalmologists who do not perform incisional glaucoma surgery increased at average annual rates of 1.6% (p<0.0002) and 3.3% (p<0.0001), respectively. In contrast, no significant growth in the rate of glaucoma consultations or follow up visits provided by glaucoma surgeons was observed (0.8%/year [p=0.2] for consultations; 0.2%/year [p=0.6] for follow up visits). Between 2000 and 2010, the rate of laser trabeculoplasty procedures provided by ophthalmologists who do not perform incisional glaucoma surgery increased 19.3% annually (p<0.0001), while growth among glaucoma surgeons was more modest (annual growth of 9.2% [p=0.0002]).Conclusions: While subspecialization is a growing reality in most areas of medicine, we found that the provision of clinic-based glaucoma care remains dependent on ophthalmologists that do not perform incisional glaucoma surgery. With increasing focus on integrated care, these findings will have important implications for residency education programs and their accrediting bodies and will inform decisions of health care policy makers, hospitals and academic departments.
Comparison of refractive stability after non-toric versus toric intraocular lens implantation during cataract surgery – Accepted Manuscript
Abstract: Purpose: To compare refractive state changes in eyes implanted with toric intraocular lenses (IOLs) versus non-toric IOLs, after cataract extraction.Design: Retrospective, comparative.Methods: In a single-institution, 121 eyes underwent phacoemulsification and implantation with either non-toric IOLs (AcrySof® IQ SN60WF) or toric IOLs (AcrySof® Toric IOL). The spherical value, cylindrical value, spherical equivalent (SE) of refractive error, and visual acuity were measured preoperatively and 1, 3, and 6 months after surgery. Main outcome measures were the pattern of changes of spherical, cylindrical, and SE values based on postoperative time, between different IOL types.Results: The groups included patients who underwent surgery with SN60WF (Group I), SA6AT3 (Group II-3), SA6AT4 (Group II-4), and SA6AT5 lens (Group II-5) containing 37, 29, 23, and 32 eyes, respectively. The cylindrical value was significantly decreased in all groups (p<0.05). Before surgery, the SE of refractive errors was estimated as -0.21, -0.10, -0.20, and -0.22 in respective groups. The actual remaining SE values were -0.19, -0.24, -0.42, and -0.56 at 1 month; -0.17, -0.26, -0.57, and -0.64 at 3 months; and -0.17, -0.26, -0.70, and -0.74 at 6 months postoperatively, respectively. The follow-up SE values in groups I and II-3 were similar (p>0.05 in both groups); however, significant myopic changes were observed in Groups II-4 and II-5 after surgery, versus Group I (p<0.05).Conclusion: Selection of toric IOLs for cataract surgery requires a refined formula to precisely determine necessary IOL power, especially in cases with high levels of astigmatism, to reliably and accurately prevent myopic outcomes.
Comparison of Wide-Field Fluorescein Angiography and Nine-Field Montage Angiography in Uveitis – Accepted Manuscript
Abstract: Purpose: To qualitatively and quantitatively compare Optos© fundus camera fluorescein angiographic images of retinal vascular leakage with 9-field montage Topcon© fluorescein angiography (FA) images in patients with uveitis. We hypothesized that Optos images reveal more leakage in uveitis patients.Design: Retrospective, observational case series.Methods: Images of all uveitis patients imaged with same-sitting Optos FA and 9-field montage FA during a 9 month period at a single institution (52 eyes of 31 patients) were graded for the total area of retinal vascular leakage. The main outcome measure was area of fluorescein leakage.Results: The area of apparent FA leakage was greater in Optos images than in 9-field montage images (median 22.5 mm2 vs. 4.8 mm2, P<0.0001). Twenty-two of 49 (45%) eyes with gradable photos had at least 25% more leakage on the Optos image than on the montage image. Two (4.1%) had at least 25% less leakage on Optos, and 25 (51%) were similar between the two modalities. Two eyes had no apparent retinal vascular leakage on 9-field montage but were found to have apparent leakage on Optos images. Twenty-three of the 49 eyes had posterior pole leakage, and of these 17 (73.9%) showed more posterior pole leakage on the Optos image. A single 200 degree Optos FA image captured a mean 1.50x the area captured by montage photography.Conclusion: More retinal vascular pathology, both in the periphery and the posterior pole, is seen with Optos FA in uveitis patients when compared with 9-field montage. The clinical implications of Optos FA findings have yet to be determined.
HLA-DR, DQ Class II DNA Typing in Pediatric Panuveitis and Tubulointerstitial Nephritis and Uveitis (TINU) – Accepted Manuscript
Abstract: Purpose: To describe chorioretinal lesions in pediatric uveitis that are strongly associated with the HLA-DR,DQ Class II type associated with tubulointerstitial nephritis and uveitis (TINU).Design: Retrospective, observational case series.Methods: Results: Fourteen of the 15 patients (93%) with otherwise unexplained pediatric panuveitis typed HLA-DRB1*01-HLA-DQB1*05. Eleven of 15 (73.3%) had bilateral sharply demarcated, usually inferior, 200-300 micron spots of chorioretinal atrophy, and 4 of 15 (27.7%) had bilateral clusters of 500-750 micron poorly defined orange choroidal lesions without overlying atrophy of the retinal pigment epithelium. None had interstitial nephritis. Four of the 6 definite TINU cases had Class II typing and TINU risk alleles; all 6 had bilateral panuveitis. The frequency of risk alleles was statistically higher in pediatric panuveitis than in the North American population, and in non-panuveitis pediatric uveitis patients assumed to have the North American HLA distribution (P<.0001, Fischer’s Exact). Positive likelihood ratios were 9.92 to 5.18 depending on assumptions regarding pre-test probability of disease.Conclusions: Recognition of characteristic chorioretinal lesions in otherwise unexplained pediatric panuveitis, supported by selective HLA Class II DNA typing, is useful in narrowing diagnostic possibilities and directing further evaluations. Panuveitis is under appreciated as a manifestation of TINU.
Lateral Rectus Superior Compartment Palsy – Corrected Proof
Purpose: To employ magnetic resonance imaging (MRI) to seek evidence of compartmental lateral rectus atrophy consistent with a lesion involving selective denervation of only 1 of the 2 neuromuscular compartments of the lateral rectus.Design: Prospective observational case-control series.Methods: At a single institution, surface coil coronal MRI was obtained at 312 μm resolution in quasi-coronal planes 2 mm thick throughout the orbit in 20 normal volunteers and 18 patients with unilateral lateral rectus palsy fixated monocularly on a target placed in central gaze. Maximum cross sections and posterior volumes of the superior and inferior lateral rectus compartments were computed and correlated with clinical findings.Results: Twelve patients with lateral rectus palsy demonstrated symmetric, highly significant 40% reductions in maximum cross sections and 50% reductions in posterior volumes from normal for both compartments (P < 10−6 for all comparisons). Six patients with lateral rectus palsy had similar significant but asymmetric reductions in those measures only for the superior compartment of the affected lateral rectus (P < 10−4 for all comparisons), with insignificant 20%-30% reductions for the inferior compartment (P > 0.2 for all comparisons).Conclusions: A subset of patients with clinical lateral rectus palsy may have palsy limited to the superior compartment. Paralytic esotropia may be caused by lateral rectus superior compartment palsy despite an intact lateral rectus inferior compartment. This finding is consistent with evidence supporting independent innervation of the 2 lateral rectus neuromuscular compartments.
Author Reply – Corrected Proof
Dr Fellman’s thoughtful comments allow for an opportunity to provide clarification with regard to the message conveyed in the editorial, “Things Go Better With Cataract Surgery.” First and foremost, I agree with Dr Fellman that blebless surgery is …
The Steroids for Corneal Ulcers Trial (SCUT): Secondary 12-Month Clinical Outcomes of a Randomized Controlled Trial – Corrected Proof
Purpose: To determine whether topical corticosteroids as adjunctive therapy for bacterial keratitis improves long-term clinical outcomes.Design: Randomized, placebo-controlled, double-masked clinical trial.Methods: This multicenter trial compared 1.0% …
Atropine for the Treatment of Childhood Myopia: Changes after Stopping Atropine 0.01%, 0.1% and 0.5% – Corrected Proof
Purpose: To study the change in spherical equivalent and other ocular parameters 1 year after stopping the administration of atropine.Design: Prospective randomized double-masked clinical trial.Methods: We assigned 400 myopic children, 6 to 12 years of age, to receive atropine 0.5%, 0.1% or 0.01% for 24 months, after which medication was stopped. Parents and children gave informed consent to participate in the research. Children were reviewed at 26, 32 and 36 months, and changes in cycloplegic spherical equivalent (SE), axial length (AL), visual acuity, pupil size, and accommodation were assessed.Results: Of the children, 356 (89%) entered into the washout phase. At entry, there was no significant difference in age, gender, SE, or AL among the children in the various atropine groups. Over the following 12 months, myopic progression was greater in the 0.5% eyes (−0.87 ± 0.52 D), compared to the 0.1% (−0.68 ± 0.45 D) and 0.01% eyes (−0.28 ± 0.33 D, P < 0.001). AL growth was also greater in the 0.5% (0.35 ± 0.20 mm) and 0.1% (0.33 ± 0.18 mm) eyes, compared to the 0.01% eyes (0.19 ± 0.13 mm, P < 0.001). Pupil size and near visual acuity returned to pre-atropine levels in all groups, but accommodation at 36 months was less in the 0.5% eyes (13.24 ± 2.72 D) compared to the 0.1% (14.45 ± 2.61 D) and 0.01% eyes (14.04 ± 2.90 D, P < 0.001). The overall increase in SE over the entire 36 months in the 0.5%, 0.1% and 0.01% groups was −1.15 ± 0.81 D, −1.04 ± 0.83 D and −0.72 ± 0.72 D, respectively (P < 0.001).Conclusion: There was a myopic rebound after atropine was stopped, and it was greater in eyes that had received 0.5% and 0.1% atropine. The 0.01% atropine effect, however, was more modulated and sustained.
Tear Meniscus Dimensions in Tear Dysfunction and Their Correlation With Clinical Parameters – Corrected Proof
Purpose: To evaluate relationships between tear meniscus dimensions and parameters of ocular surface disease in a variety of tear dysfunction conditions.Design: Single-institution prospective observational study.Methods: This study from the Baylor College of Medicine included 128 eyes of 64 subjects. Cross-sectional lower tear meniscus height and tear meniscus area were measured using optical coherence tomography and were compared with tear break-up time (TBUT), corneal staining, conjunctival staining, and an irritation symptom questionnaire (Ocular Surface Disease Index). Study groups included meibomian gland disease (MGD), aqueous tear deficiency (ATD), Sjögren syndrome, non–Sjögren syndrome ATD, and control subjects. Statistical analyses were performed using the Pearson correlation and Student’s t test.Results: When compared with mean tear meniscus height in controls (345 μm), mean tear meniscus height was lower in all tear dysfunction (234 μm; P = .0057), ATD (210 μm; P = .0016), and Sjögren syndrome groups (171 μm; P = .0054). For tear meniscus height ≤210 μm, relative risk ratio for developing corneal staining ≥10 was 4.65. Tear meniscus height correlated with corneal staining for all subjects (R = −0.32; P = .0008), MGD (R = +0.40; P = .059), and ATD (R = −0.36; P = .04). Tear meniscus area showed similar trends in MGD (R = +0.55; P = .006) and ATD (R = −0.40; P = .018). Tear meniscus height correlated with TBUT for all subjects (R = +0.39; P < .0001) and ATD (R = +0.37; P = .018).Conclusions: In tear dysfunction conditions, lower tear volume correlates with worse corneal epithelial disease in ATD and Sjögren syndrome, conditions with lacrimal gland dysfunction. In contrast, higher tear volume is associated with corneal epithelial disease in MGD. These findings may improve the ability to identify patients at risk for corneal epithelial disease.
Visual Acuity Deficits in Children With Nystagmus and Down Syndrome – Corrected Proof
Purpose: To investigate the association between visual acuity deficits and fixation instability in children with Down syndrome and nystagmus.Design: Prospective cross-sectional study.Methods: setting: Institutional. study population:Sixteen children (a…
Lack of Polypoidal Lesions in Patients with Myopic Choroidal Neovascularization as Evaluated by Indocyanine Green Angiography – Corrected Proof
Objective: To investigate the prevalence of polypoidal choroidal vasculopathy (PCV) in patients with myopic choroidal neovascularization (CNV) using indocyanine green angiography (ICGA).Design: Retrospective cross-sectional study.Methods: A total of 29…
Increased Risk of Parkinson Disease Following a Diagnosis of Neovascular Age-Related Macular Degeneration: A Retrospective Cohort Study – Corrected Proof
Purpose: To investigate the risk for Parkinson disease during a 3-year follow-up period after a diagnosis of neovascular age-related macular degeneration (AMD) using a nationwide population-based dataset in Taiwan.Design: A retrospective matched-cohort study.Methods: We identified 877subjects with neovascular AMD as the study cohort and randomly selected 8770 subjects for a comparison cohort. Each subject was individually followed for a 3-year period to identify those who subsequently developed Parkinson disease. Stratified Cox proportional hazard regressions were performed as a means of comparing the 3-year risk of subsequent Parkinson disease between the study and comparison cohorts.Results: The incidence rate of Parkinson disease was 5.32 (95% confidence interval [CI]: 3.03-8.72) per 1000 person-years in patients with neovascular AMD and 2.09 (95% CI: 1.59-2.70) per 1000 person-years in comparison patients. The log-rank test indicated that subjects with neovascular AMD had a significantly lower 3-year Parkinson disease–free survival rate than comparison subjects (P < .001). After censoring cases in which patients died during the follow-up period and adjusting for monthly income, geographic region, hypertension, diabetes, hyperlipidemia, and coronary heart disease, the hazard ratio of Parkinson disease during the 3-year follow-up period for subjects with neovascular AMD was 2.57 (95% CI: 1.42-4.64) that of comparison subjects.Conclusion: In this study, subjects with neovascular AMD were found to be at a significant risk of Parkinson disease during a 3-year follow-up period after their diagnosis among Taiwanese Chinese. Further study is needed to confirm our findings and explore the underlying pathomechanism.
Distribution of Retinal Layer Atrophy in Patients With Parkinson Disease and Association With Disease Severity and Duration – Corrected Proof
Purpose: To evaluate the thickness of the 10 retinal layers in the paramacular area of Parkinson disease patients using a new segmentation technology of optical coherence tomography (OCT) to examine whether the thickness of specific layers predicts neurodegeneration or Parkinson disease severity.Design: Observational prospective study.Methods: Parkinson disease patients (n = 129) and age-matched healthy subjects (n = 129) were enrolled. The Spectralis OCT system was used to automatically segment all retinal layers in a parafoveal scan using the new segmentation application prototype. Mean thickness of each layer was calculated and compared between Parkinson disease patients and healthy subjects, and between Parkinson disease patients with disease durations of less than or at least 10 years. A correlation analysis was performed to evaluate the association between retinal layer thickness, duration of disease, and Parkinson disease severity. Logistic regression analysis was performed to determine the most sensitive layer for predicting axonal atrophy.Results: Parkinson disease patients showed statistically significant reduced thickness in the retinal nerve fiber, ganglion cell, inner plexiform, and outer plexiform layers and increased thickness in the inner nuclear layer compared with healthy subjects (P < .05). The inner retinal layers were more affected in Parkinson disease patients with long disease duration. The ganglion cell layer thickness was inversely correlated with disease duration and Parkinson disease severity, and was predictive of axonal damage in Parkinson disease patients.Conclusions: The segmentation application of the Spectralis OCT revealed retinal layer atrophy in Parkinson disease patients, especially in the inner layers of patients with long disease duration. Ganglion cell layer reduction was associated with increased axonal damage.
Autoimmune Retinopathy – Corrected Proof
Purpose: To provide a detailed review of current clinical guidelines for the diagnosis, work-up and treatment of autoimmune retinopathy and to preview briefly possible future therapies.Design: Perspective based on literature review and clinical experti…
Prospective Masked Comparison of Intraoperative Floppy Iris Syndrome Severity with Tamsulosin versus Alfuzosin – Corrected Proof
Objective: To determine whether severe intraoperative floppy iris syndrome (IFIS) is more or equally likely with tamsulosin or alfuzosin.Design: Prospective, masked, multicenter, cross-sectional study.Participants and Controls: Consecutive patients tak…
The Effect of Colored Overlays on Reading Performance in Infantile Nystagmus – Corrected Proof
Infantile nystagmus (IN) is an involuntary oscillations of the eyes with onset within 6 months from birth. It can result in vision loss owing to constant retinal motion and lead to significant psychosocial problems. Recent studies have described readin…
Vitrectomy with Internal Limiting Membrane Peeling versus No Peeling for Idiopathic Full-Thickness Macular Hole – Corrected Proof
Objective: To determine whether internal limiting membrane (ILM) peeling improves anatomic and functional outcomes of full-thickness macular hole (FTMH) surgery when compared with the no-peeling technique.Design: Systematic review and individual participant data (IPD) meta-analysis undertaken under the auspices of the Cochrane Eyes and Vision Group. Only randomized controlled trials (RCTs) were included.Participants and Controls: Patients with idiopathic stage 2, 3, and 4 FTMH undergoing vitrectomy with or without ILM peeling.Intervention: Macular hole surgery, including vitrectomy and gas endotamponade with or without ILM peeling.Main Outcome Measures: Primary outcome was best-corrected distance visual acuity (BCdVA) at 6 months postoperatively. Secondary outcomes were BCdVA at 3 and 12 months; best-corrected near visual acuity (BCnVA) at 3, 6, and 12 months; primary (after a single surgery) and final (after >1 surgery) macular hole closure; need for additional surgical interventions; intraoperative and postoperative complications; patient-reported outcomes (PROs) (EuroQol-5D and Vision Function Questionnaire-25 scores at 6 months); and cost-effectiveness.Results: Four RCTs were identified and included in the review. All RCTs were included in the meta-analysis; IPD were obtained from 3 of the 4 RCTs. No evidence of a difference in BCdVA at 6 months was detected (mean difference, −0.04; 95% confidence interval [CI], −0.12 to 0.03; P = 0.27); however, there was evidence of a difference in BCdVA at 3 months favoring ILM peeling (mean difference, −0.09; 95% CI, −0.17 to −0.02; P = 0.02). There was evidence of an effect favoring ILM peeling with regard to primary (odds ratio [OR], 9.27; 95% CI, 4.98–17.24; P < 0.00001) and final macular hole closure (OR, 3.99; 95% CI, 1.63–9.75; P = 0.02) and less requirement for additional surgery (OR, 0.11; 95% CI, 0.05–0.23; P < 0.00001), with no evidence of a difference between groups with regard to intraoperative or postoperative complications or PROs. The ILM peeling was found to be highly cost-effective.Conclusions: Available evidence supports ILM peeling as the treatment of choice for patients with idiopathic stage 2, 3, and 4 FTMH.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Defining the Limits of Normal Conjunctival Fornix Anatomy in a Healthy South Asian Population – Corrected Proof
Purpose: Quantifying the extent of conjunctival fibrosis for documentation of progression in conjunctival scarring disease is a clinical challenge. Measurement of forniceal foreshortening facilitates monitoring of these disorders. This study aims (1) to define the limits of the normal human conjunctival fornices and how these alter with age and (2) to provide normative data for upper and lower fornix depths (FDs) and fornix intercanthal distance (FICD) within a healthy South Asian, racially distinct population.Design: Epidemiologic, cross-sectional study.Participants: A total of 240 subjects with national origins from South Asia, with no known ocular history and normal adnexal and conjunctival examination, aged 20 to 80 years.Methods: An FICD modification of a custom-designed fornix depth measurer (FDM) was validated and used for measurement of both lower and upper FDs together with FICDs in 480 healthy eyes with no ocular comorbidities. Data were analyzed using repeated-measures analysis of variance and presented as means with 95% confidence intervals (CIs).Main Outcome Measures: Mean lower and upper FDs and FICD for the entire cohort, stratified according to age decade and sex.Results: For this South Asian population, the overall upper and lower FDs were 15.3 mm (95% CI, 14.9–15.6) and 10.9 mm (95% CI, 10.7–11.1), respectively, with FICD defined as 32.9 mm (95% CI, 32.5–33.4) (upper) and 31.7 mm (95% CI, 31.3–32.1) (lower). With increasing age, a progressive reduction of all measured parameters (P < 0.001) was noted, with female subjects having significantly shallower fornices (upper FD, P < 0.001; lower FD, P < 0.001; upper FICD, P = 0.081; and lower FICD, P = 0.015).Conclusions: This is the first study to define the limits of normal upper FD and FICDs in any population group. Our study demonstrates sex variations and progressive conjunctival shrinkage with age. Although it provides important, objective data for normal forniceal anatomy, further study is recommended in other populations to confirm the generalizability of these data or to enable normal comparative datasets for the assessment of conjunctival scarring disorders among all anthropological groups.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.