Effective field of view of wide-field fundus photography in the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP).

Five-field 130° wide-angle imaging is the standard of care for retinopathy of prematurity (ROP) screening with an ideal hypothetical composite field-of-view (FOV) of 180°. We hypothesized that in many real-world scenarios the effective composite FOV is considerably less than ideal. This observational retrospective study analyzed the effective FOV of fundus photos of patients screened for ROP as part of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) initiative. Five fundus photos were selected from each eye per image session. Effective FOV was defined as the largest circular area centered on the optic disc that encompassed retina in each of the four cardinal views. Seventy-three subjects were analyzed, 35 without ROP and 34 with ROP. Mean effective FOV was 144.55 ± 6.62° ranging from 130.00 to 153.71°. Effective FOV was not correlated with the presence or absence of ROP, gestational age, birth weight, or postmenstrual age. Mean effective FOV was wider in males compared to females. Standard five-field 130° fundus photos yielded an average effective FOV of 144.54° in the SUNDROP cohort. This implies that an imaging FOV during ROP screening considerably less than the hypothetical ideal of 180° is sufficient for detecting treatment warranted ROP.

Displacement of submacular hemorrhage with intravitreal tissue plasminogen activator following 27 gauge transvitreal fine needle aspiration biopsy for choroidal melanoma.

PURPOSE: To describe the management of submacular hemorrhage (SMH), a vision threatening complication following transvitreal choroidal biopsy, with intravitreal tissue plasminogen activator (tPA) and pure perfluoropropane (C3F8) gas bubble injection. OBSERVATIONS: A 53 year old female with choroidal melanoma of the left eye underwent iodine-125 plaque brachytherapy placement and 27 gauge transvitreal fine needle aspiration choroidal biopsy for gene expression profiling. On postoperative day 2, large SMH was identified on dilated fundus examination. At the time of plaque brachytherapy removal, intravitreal tPA and pure C3F8 gas bubble injection with post operative positioning was also performed to attempt displacement of SMH. At postoperative month 1 following tPA and gas bubble displacement, the SMH was completely displaced inferotemporally outside of the macula and visual acuity improved from 20/70 at postoperative week 1 to 20/25 at postoperative month 1. CONCLUSIONS AND IMPORTANCE: Subretinal hemorrhage can be a complication of transvitreal choroidal tumor biopsy but early detection and prompt treatment can result in good visual outcomes.

Development and Preliminary Validation of a Virtual Reality Approach for Measurement of Torsional Strabismus.

BACKGROUND: Double Maddox rod (DMR), the gold-standard method for in-office measurement of cyclodeviation, requires an examiner and specialized equipment. The objective of this study was to develop a virtual reality (VR) technique for measurement of cyclodeviation and validate this against the DMR. METHODS: A VR-DMR was implemented using a smartphone and commercially available VR viewer. The app displayed a line to each eye and accepted touch inputs from the user to rotate the lines into perceived alignment. VR-DMR cyclodeviation measurements were compared with traditional DMR (T-DMR) cyclodeviation measurements in adults with and without strabismus and children without strabismus. RESULTS: Thirty-one subjects were studied (age 5-88 years, 20 with strabismus). VR-DMR had similar test-retest reliability as T-DMR. VR-DMR was highly correlated with T-DMR (r2 = 0.94, linear regression slope 1.12) with a slight positive bias (linear regression y intercept 1°). VR-DMR was preferred by 54% of subjects with 29% having no preference. CONCLUSIONS: A VR method of ocular cyclodeviation measurement using sensory techniques was implemented using commercially available hardware. VR measurements compared favorably with gold-standard DMR measurements, and user feedback was positive. The VR methodology has application for in office and home use by nonexperts for purposes of strabismus monitoring.

Conserved regression patterns of retinopathy of prematurity after intravitreal ranibizumab: A class effect.

PURPOSE: To determine if fluorescein angiographic (FA) findings after intravitreal ranibizumab (IVR) for retinopathy of prematurity (ROP) conform to a class effect previously described with bevacizumab. METHODS: Single-center retrospective case series of all infants treated with 0.2 mg (0.02 mL) IVR for Type 1 ROP from July 2016 to November 2018. FA were obtained at 40, 52, 62, and 72 weeks of postmenstrual age (PMA) using wide-angle photography. FA images were analyzed and the peripheral avascular areas measured with ImageJ using a reference disc diameter (DD). Based on the extent of the avascular area and tortuosity of the retinal vessels all eyes were classified into four categories: complete vascular maturity (vascularization within 2 DD of the ora serrata), VAA (avascular area >2 DD of the ora serrata), VAT (avascular area >2 DD of the ora serrata and posterior tortuosity), and reactivation (recurrence of stage disease). RESULTS: About 13 infants were enrolled and 24 eyes were available in this study. None of the eyes reached complete vascular maturity at an average PMA of 60 weeks, 7 (29%) eyes presented with VAA, 8 (33%) with VAT, and 9 (37.5%) reactivated. The reactivated eyes presented with the largest area of peripheral ischemia, followed by the VAT and then the VAA groups (p = 0.02). CONCLUSION: IVR conforms to the previously described regression patterns following intravitreal bevacizumab for ROP indicative of a class effect. Follow-up using FA might help to optimize the management of these infants after injection of the drug.

Comparison of non-absorbable silk and absorbable polyglactin sutures for external ptosis repair.

Purpose: The authors compare the outcomes and revision rates for external levator aponeurotic advancement for the treatment of involutional ptosis using non-absorbable silk and absorbable polyglactin sutures.Methods: An IRB-approved retrospective chart review identified 121 patients who underwent external levator advancement for involutional ptosis between 2015 and 2016 by the senior author (JBH).  All patients underwent ptosis repair using either 5-0 polyglactin 910 on a S-14 spatulated needle or 6-0 silk on a G-1 reverse cutting needle for the aponeurotic advancement. Ptosis etiologies other than involutional ptosis were excluded. Patients with >0.5 mm of upper lid height asymmetry post-operatively underwent surgical adjustment. Demographics, clinical findings and revision rates were collected and analyzed from follow-up visits.Results: 116 patients (190 eyelids) met inclusion criteria. Fewer ptosis repairs performed using silk sutures necessitated adjustment when compared to those using polyglactin (1/73 [1.4%] vs. 14/117 [12.0%], p = 0.010). Silk direct connection sutures had no better stability than polyglactin direct connection sutures (p = 0.16), but silk hang-back sutures were significantly superior to polyglactin hang-back sutures (p = 0.035).  Thirteen out of fifteen (86.7%) revisions were advancements to raise the eyelid, while two (13.3%) were recessions.Conclusion: Non-absorbable silk suture may be superior to absorbable polyglactin, necessitating fewer surgical revisions. Silk demonstrated superiority to polyglactin when a hang-back suture was employed. Since the need to place direct or hang-back sutures cannot be made pre-operatively, the authors modified their technique to utilize silk sutures for external aponeurotic ptosis repair.

Risk of Endophthalmitis in Boston Type 1 Keratoprosthesis Combined with Vitrectomy and Silicone Oil Insertion.

PURPOSE: To identify the incidence of endophthalmitis and visual outcomes in eyes with Boston type 1 keratoprosthesis combined with pars plana vitrectomy and silicone oil insertion (KPro + PPV + SOI) as compared to eyes receiving Boston type 1 keratoprosthesis (KPro) alone. PATIENTS AND METHODS: Retrospective chart review of 29 eyes of 27 patients with KPro having at least 12-month follow-up. Thirteen of these eyes had hypotony and/or retinal detachment in addition to corneal pathology and thus received KPro + PPV + SOI. Polymyxin-trimethoprim with a quinolone was used as chronic topical antibiotic prophylaxis in both groups after the first postoperative month. Outcome measures recorded at the 1-, 3-, 6-, 12-, and 24-month follow-up visits included best-corrected visual acuity (BCVA) and rates of postoperative complications. RESULTS: All the patients had completed 24-month follow-up except one case in the KPro group who lost to follow-up after 12-month visit. In the KPro + PPV + SOI group, no eyes had developed endophthalmitis by the 24-month follow-up visit versus 5 eyes of 5 patients in the uncombined KPro group (P=0.048). The 2-year cumulative endophthalmitis incidence was 31.2% in the KPro group versus zero in the KPro + PPV + SOI group (P=0.030). Four of these 5 eyes had vitreous taps with positive cultures; 2 were positive with Staphylococcus aureus, 1 with coagulase-negative staphylococci, and 1 with Streptococcus pneumoniae. Other complications included KPro extrusion (1 in each group), retinal detachment (2 in the KPro and 1 in the KPro + PPV + SOI group), newly developed glaucoma (2 in each group), and retroprosthetic membrane (9 in the KPro and 5 in the KPro + PPV + SOI group). The KPro group had better average preoperative BCVA compared to those of the KPro + PPV + SOI group (-2.29 ± 0.72 LogMAR, versus -2.95 ± 0.30 LogMAR; P=0.004). No statistically significant difference in BCVA was noted in subsequent follow-up visits. CONCLUSION: The addition of PPV and SOI to the KPro implantation in the eyes with corneal pathology, as well as hypotony and/or retinal detachment, is a safe and effective procedure for visual rehabilitation. Pars plana vitrectomy and silicone oil insertion may have a protective effect against the development of postoperative endophthalmitis in eyes receiving KPro.

Evaluating New Ophthalmic Digital Devices for Safety and Effectiveness in the Context of Rapid Technological Development.

IMPORTANCE: The US Food and Drug Administration's medical device regulatory pathway was initially conceived with hardware devices in mind. The emerging market for ophthalmic digital devices necessitates an evolution of this paradigm. OBJECTIVES: To facilitate innovation in ophthalmic digital health with attention to safety and effectiveness. EVIDENCE REVIEW: This article presents a summary of the presentations, discussions, and literature review that occurred during a joint Ophthalmic Digital Health workshop of the American Academy of Ophthalmology, the American Academy of Pediatrics, the American Association for Pediatric Ophthalmology and Strabismus, the American Society of Cataract and Refractive Surgery, the American Society of Retina Specialists, the Byers Eye Institute at Stanford and the US Food and Drug Administration. FINDINGS: Criterion standards and expert graders are critically important in the evaluation of automated systems and telemedicine platforms. Training at all levels is important for the safe and effective operation of digital health devices. The risks associated with automation are substantially increased in rapidly progressive diseases. Cybersecurity and patient privacy warrant meticulous attention. CONCLUSIONS AND RELEVANCE: With appropriate attention to safety and effectiveness, digital health technology could improve screening and treatment of ophthalmic diseases and improve access to care.

Optical Coherence Tomography Angiography Highlights Chorioretinal Lesions in Ocular Coccidioidomycosis.

A 34-year-old woman presented after recovering from a disseminated Coccidioides immitis infection of the lungs, blood, brain, and placenta. The patient was asymptomatic for visual complaints. Visual acuity was 20/20 in both eyes. Fundus examination demonstrated bilateral chorioretinal infiltrates worse in the left eye. Fluorescein angiography (FA) was unable to be performed as the patient was breastfeeding, prompting the use of optical coherence tomography angiography (OCTA) imaging to further investigate the infiltrates. OCTA imaging was able to detect all visualized chorioretinal infiltrates and showed an additional non-visualized deep choroidal lesion. OCTA is a valuable tool in detecting chorioretinal lesions when FA is contraindicated. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e71-e73.].

A Spectrum of Regression Following Intravitreal Bevacizumab in Retinopathy of Prematurity.

PURPOSE: To describe an improved understanding of the regression patterns following off-label intravitreal bevacizumab (IVB) treatment for retinopathy of prematurity (ROP). DESIGN: Retrospective cohort study. METHODS: All infants treated with IVB for type 1 ROP at a single institution from June 2013 to March 2018 were retrospectively reviewed and the amount of retinal nonperfusion on fluorescein angiogram was calculated. RESULTS: In the 92 eyes of 46 patients analyzed, only 3 eyes (3.3%) reached full vascular maturity. Of the 89 eyes not reaching maturity, 39 eyes (43.8%) had vascular arrest alone (VAA), 34 eyes (38.2%) had vascular arrest with persistent tortuosity (VAT), and 16 eyes (18.0%) had ROP reactivation. Those eyes that reactivated were more likely to be initially classified as having aggressive posterior ROP (P = .004) and of Asian ethnicity (P = .008). There were greater areas of ischemia in eyes with reactivation as compared to VAT and VAA (112.1 mm2 vs 72.5 mm2 vs 56.6 mm2, respectively, P = .007). Younger gestational age at birth was found to be an independent predictor of persistent tortuosity (VAT vs VAA) in a logistic regression model. CONCLUSIONS: Incomplete vascularization following IVB is very common and is associated with a younger gestational age at birth, Asian ethnicity, and aggressive posterior ROP. The presence of tortuosity following IVB may be indicative of persistently elevated vascular endothelial growth factor levels and an early indicator of potential reactivation.

The Role of Surgeon Technique in Current Practice Patterns for Combined Ptosis and Dermatochalasis.

PURPOSE: The goal of this study is to identify and describe the role of surgical incision preference, insurance reimbursement, and geographical location on the current ptosis repair practice patterns of American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) members. METHODS: A 9-question survey was designed with surveymonkey.com and a participation link was emailed to all active ASOPRS members' email addresses in February 2015. After a reminder email, the survey was closed and the results were analyzed. There are 3 major questions the survey data is to be used answer: 1) Surgical approach preference: The first question established preferred surgical technique (internal vs. external approach) for ptosis repair. This result was/is used to stratify the remaining responses into 2 groups. 2) Functional versus cosmetic surgical indication: Three clinical scenarios were presented for a functional versus cosmetic patient for ptosis repair and blepharoplasty. 3) Location: The responses were analyzed based on location to determine any geographic bias for surgical preference. For this analysis, the US was separated into 4 regions (West, Midwest, North, and South), as defined by the United States Census Bureau; all international respondents were grouped together. RESULTS: Three hundred and ten responses were included and analyzed; 61% preferred the internal surgical approach, there was no statistical significance to geographic location (p = 0.17). Surgeons who prefer the external surgical approach (76.1%) were more likely than internal (62.5%) to include a bundled (nonreimbursed) blepharoplasty at no additional charge in the setting of functional ptosis repair (p = 0.015). Treatment plans differed significantly in both groups between functional and cosmetic patients with visually significant ptosis (Margin Reflex Distance < 1.5) and moderate dermatochalasis; with both the internal and external group electing combined surgery at a higher rate in cosmetic patients (p < 0.01 for functional vs. cosmetic within each group, and internal vs. external repair). There was no statistical difference in the timeframe for adjusting external ptosis for functional or cosmetic patients (p = 0.79). More surgeons use nonabsorbable closure for cosmetic blepharoplasty patients (68.7%) than for functional (54.1%) surgery patients (p < 0.01). CONCLUSION: Previous studies have documented the immediate effect of Medicare reimbursement changes on the management of concurrent ptosis and dermatochalasis. This study illustrates current practice patterns for ptosis repair and blepharoplasty. The necessity of creating a separate surgical site for surgeons who prefer the internal approach to ptosis surgery to perform a functional blepharoplasty has a significant influence on surgeon's willingness to perform concurrent blepharoplasty as a nonreimbursed bundled procedure.

Automated Ptosis Measurements From Facial Photographs.

IMPORTANCE: Measurements of the margin reflex distances 1 and 2 are crucial for the surgical planning of ptosis repair and blepharoplasty. Facial photographs annotated with automated measurements of eyelid position could provide objective, accurate, and reproducible documentation of these features. OBJECTIVES: To describe a software algorithm for determining the margin reflex distances 1 and 2 from facial photographs and to evaluate its agreement with manual measurements of the margin reflex distances 1 and 2. DESIGN, SETTING, AND PARTICIPANTS: Observational study at a single-surgeon oculoplastic private practice among 55 eyes of 28 adult volunteers. The study dates were July 30, 2014, to September 12, 2014. The dates of our analysis were October 12, 2014, to June 18, 2015. MAIN OUTCOMES AND MEASURES: Agreement between manual and automated measurements of the margin reflex distances 1 and 2. RESULTS: Among 55 eyes of 28 participants, automated margin reflex distance 1 measurements were strongly correlated with manual measurements (r = 0.97; 95% CI, r = 0.95 to r = 0.98; P < .001). The bias of automated margin reflex distance 1 measurements was 0.03 mm (95% CI, -0.06 to 0.12 mm), with 95% confidence limits of -0.66 and 0.71 mm. Automated margin reflex distance 2 measurements were strongly correlated with manual measurements (r = 0.96; 95% CI, r = 0.93 to r = 0.98; P < .001). The bias of automated margin reflex distance 2 measurements was 0.13 mm (95% CI, 0.03-0.22 mm), with 95% confidence limits of -0.54 and 0.80 mm. CONCLUSIONS AND RELEVANCE: Automated ptosis measurements produced by our software algorithm compare favorably with manually performed clinical measurements. An automated, photography-based system could provide an archival and highly reproducible means for obtaining the margin reflex distances 1 and 2 and other facial morphometric data.

Portomesenteric venous thrombosis following major colon and rectal surgery: incidence and risk factors.

BACKGROUND: Portomesenteric venous thrombosis (PMVT) is an uncommon complication of abdominal surgery. The objective of this study was to assess PMVT risk factor profiles and patient outcomes after colorectal surgery. METHODS: A single center retrospective review of patients undergoing colorectal surgery was performed (2007-2012). PMVT was defined as thrombus within the portal, splenic, or superior mesenteric vein on computed tomography (CT). Inferior mesenteric vein thrombosis was excluded. Independent samples t test was used to compare data variables between PMVT and non-PMVT patients. Univariate and multivariate logistic regression analyses were used to assess PMVT risk factors. RESULTS: There were 1,224 patients included (mean age 62 years, male = 566). Elective bowel resection was performed for colon carcinoma (n = 302), rectal carcinoma (n = 112), ulcerative colitis (n = 125), Crohn's disease (n = 78), polyps (n = 117), and diverticulitis (n = 215). Patients undergoing gynecological resections and emergent laparotomies were included (n = 275). Thirty-six patients (3%) were diagnosed with PMVT by CT: 17/36 on initial presentation and 19/36 by expert radiologist review. Patients with PMVT were younger (53 vs. 62 years, p = 0.001) with higher BMI (30.5 vs. 26.7, p < 0.001) and thrombocytosis (464 vs. 306, p < 0.001) compared to patients without PMVT. Univariate logistic regression identified younger age (p < 0.001), obesity (p < 0.001), ulcerative colitis (p < 0.001), thrombocytosis, (p < 0.001) and proctocolectomy as significant predictors of PMVT. Stepwise multivariate logistic regression identified that obesity (p < 0.001), thrombocytosis, (p < 0.001) and restorative proctocolectomy (p = 0.001) were still significant predictors. No patients in the PMVT group suffered bowel infarction and no related mortalities occurred. Thirty-day readmission rates were higher in the PMVT group (53% vs. 17%, p < 0.01). CONCLUSION: BMI ≥ 30 kg/m(2), thrombocytosis, and restorative proctocolectomy were significant predictors of PMVT. Initial diagnostic studies showed a PMVT rate of 1.4%; however, after expert focused radiologic review, the actual rate was 3%. Thus, the diagnosis of PMVT is difficult and readmission after colorectal surgery should prompt its consideration.

Light transmittance of 1-piece hydrophobic acrylic intraocular lenses with surface light scattering removed from cadaver eyes.

PURPOSE: To assess the potential effect of surface light scattering on light transmittance of 1-piece hydrophobic acrylic intraocular lenses (IOLs) with or without a blue-light filter. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Intraocular lenses were obtained from human cadavers (49 IOLs total; 36 with blue-light filter) and from finished-goods inventory (controls). The IOLs were removed from cadaver eyes and the power and model matched to unused controls. After surface proteins were removed, the IOLs were hydrated for 24 hours at room temperature. Surface light scattering was measured with a Scheimpflug camera (EAS-1000 Anterior Segment Analysis System). Light transmittance was measured with a Lambda 35 UV/Vis spectrophotometer (single-beam configuration; RSA-PE-20 integrating sphere). RESULTS: Hydrated scatter values ranged from 4.8 to 202.5 computer-compatible tape (CCT) units for explanted IOLs with blue-light filter and 1.5 to 11.8 CCT units for controls; values ranged from 6.0 to 137.5 CCT units for explanted IOLs without a blue-light filter and 3.5 to 9.6 CCT units for controls. In both groups, there was a tendency toward increasing scatter values with increasing postoperative time. No differences in light transmittance were observed between explanted IOLs and controls in both groups (IOLs with blue-light filter: P=.407; IOL with no blue-light filter: P=.487; both paired t test). CONCLUSIONS: Although surface light scattering of explanted IOLs was significantly higher than that of controls and appeared to increase with time, no effect was observed on light transmittance of 1-piece hydrophobic acrylic IOLs with or without a blue-light filter.

Capsular bag opacification with a new accommodating intraocular lens.

PURPOSE: To evaluate the biocompatibility and capsular bag opacification of an accommodating intraocular lens (IOL) containing large haptic elements that separate the anterior and posterior capsules. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Bilateral phacoemulsification with IOL implantation was performed in 6 New Zealand rabbits. Each animal received a study (accommodating) IOL and a control (1-piece hydrophobic acrylic) IOL. Eyes were examined at the slitlamp from 1 day through 6 weeks postoperatively. The globes were then enucleated and evaluated grossly. Capsular bag opacification was scored from the posterior aspect (Miyake-Apple view). The eyes were then processed for complete histopathologic evaluation. RESULTS: At 6 weeks, the mean posterior capsule opacification (PCO) clinical score was 0.5 ± 0.3 (SD) in the study group and 3.0 ± 0.9 in the control group (P=.001, 2-tail paired t test). Anterior capsule opacification was practically absent in the study group and mild in the control group. Miyake-Apple posterior view showed a mean central PCO score of 0 ± 0 in the study group and 3.0 ± 1.1 in the control group (P=.001), peripheral PCO score of 0.7 ± 0.4 and 3.5 ± 0.8 (P=.0006), respectively, and Soemmerring ring score of 2.3 ± 0.8 and 7.0 ± 2.8 (P=.01), respectively. Histopathology showed no signs of toxicity in any eye. CONCLUSIONS: The study IOL maintained an expanded capsular bag secondary to the large size of the haptic elements, which appears to prevent capsular bag opacification.

Pathologic comparison of asymmetric or sulcus fixation of 3-piece intraocular lenses with square versus round anterior optic edges.

OBJECTIVE: To evaluate the pathologic findings of 3-piece intraocular lenses (IOLs) with asymmetric or sulcus fixation in pseudophakic cadaver eyes, comparing IOLs with square or round edges on the anterior optic surface. DESIGN: Comparative case series with pathology. PARTICIPANTS: A total of 661 pseudophakic cadaver eyes, obtained from eye banks within the United States, implanted with different IOLs. METHODS: Anterior segment scanning of whole eyes with a high-frequency ultrasound system or high-resolution anterior segment magnetic resonance imaging followed by gross examination. Selected eyes were processed for complete histopathologic analysis. MAIN OUTCOME MEASURES: Findings from imaging, gross, and histopathologic evaluation that could be related to out-of-the-bag fixation of the lenses. RESULTS: Of 661 pseudophakic cadaver eyes obtained, 13 had 3-piece hydrophobic acrylic IOLs with anterior and posterior square optic edges, and 14 had 3-piece lenses with anterior round edges (13 silicone lenses and 1 hydrophobic acrylic lens) without symmetric in-the-bag fixation. These 27 selected eyes were processed for complete histopathologic analysis. Gross findings in both groups were composed of IOL decentration and tilt, pigmentary dispersion within the anterior segment and on the IOL surface, and iris transillumination defects. Histopathology of the 14 eyes with 3-piece IOLs with round anterior optic edges showed mild focal disruption of the iris pigmented layer and loop protrusion/erosion in the ciliary sulcus. Additional changes observed in the 13 eyes with square anterior optic edge IOLs included iris changes, such as vacuolization, disruption and loss of the pigmented epithelial layers, iris thinning and atrophy, synechiae, and pigmentary dispersion within the trabecular meshwork. One eye also exhibited initial signs of optic nerve disc cupping. CONCLUSIONS: In this series, pathologic findings were more severe in eyes implanted with 3-piece IOLs with square anterior optic edges, suggesting that IOLs with round anterior edges are more suitable for sulcus fixation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.