Author: Am J Ophthalmol

Androgen Receptor Identification in the Diagnosis of Eyelid Sebaceous Carcinomas – Accepted Manuscript

Abstract: Purpose: To assess the role of androgen receptor detection in diagnosing eyelid sebaceous carcinomas and compare it with that of adipophilin.Design: Retrospective clinicopathologic study.Methods: Ten sebaceous carcinomas (eight invasive, two intraepithelial only) were immunohistochemically stained for androgen receptors and compared with adipophilin staining. Receptor staining was also performed on benign sebaceous tumors (a sebaceoma and an adenoma), and as controls on eyelid basal cell carcinomas, eyelid squamous cell carcinomas, conjunctival squamous dysplasias and conjunctival melanomas.Results: All eight patients with an invasive component of sebaceous carcinoma had a biopsy in which the tumor cells were diffusely androgen receptor positive (>20% of cells and usually >40%) and adipophilin positive. Eight cases displaying an intraepithelial (“pagetoid”) component of spread were also diffusely androgen receptor- and adipophilin-positive in at least one of multiple biopsies from each patient. However, in eight of 21 separate conjunctival biopsy specimens with intraepithelial cytologic atypia, adipophilin was negative. A sebaceoma and a sebaceous adenoma were also positive for both of these biomarkers. Among the controls, squamous carcinomas and melanomas were androgen receptor- and adipophilin-negative. Basal cell carcinomas displayed focal receptor positivity in fewer than 5% of cells and were adipophilin-negative.Conclusions: Androgen receptors and adipophilin can immunohistochemically separate sebaceous tumors from squamous carcinomas and melanomas, which were negative for both, and from basal cell carcinomas, which were receptor-positive in a distant minority of cells. Regarding intraepithelial (“pagetoid”) spread, androgen receptor detection was more sensitive and reliable than adipophilin in highlighting this component of the disease.

Corneal cross-linking: Intrastromal riboflavin concentration in iontophoresis-assisted imbibition versus traditional and transepithelial techniques – Accepted Manuscript

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.

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.

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.

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.

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.

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.