Long-term safety and efficacy of single-port pars plana anterior vitrectomy with limbal infusion during anterior segment surgery.

PURPOSE: To report the safety and efficacy of single-port pars plana anterior vitrectomy. SETTING: Cincinnati Eye Institute, Cincinnati, Ohio, USA. DESIGN: Retrospective case series. METHODS: Eyes that had anterior vitrectomy from September 2010 to June 2016 were electronically identified. Charts were reviewed for demographics, history of ocular trauma, underlying ocular or systemic comorbidity, surgical indications, outcomes, and postoperative complications. RESULTS: The mean postoperative follow-up was 10.9 months with a mean patient age of 62.4 years. Three hundred thirty-five eyes (97.7%) were scheduled as planned anterior vitrectomies, whereas 8 eyes (2.3%) were operated on unexpectedly after posterior capsule ruptures. Eighty-two eyes (23.9%) had a history of trauma. Twenty-five eyes (7.3%) had documented postoperative cystoid macular edema (CME), whereas 7 (2.0%) of these eyes had known preoperative CME. There were 3 eyes (0.9%) with retinal detachments and 1 eye (0.3%) with a retinal tear without detachment. There were no cases of endophthalmitis and no evidence of residual vitreous prolapse in the anterior chamber in any eye postoperatively. CONCLUSIONS: The safety and efficacy profile of a pars plana technique compared favorably against historical data for both coaxial and bimanual limbal clear corneal infusion and cutting. Sutureless pars plana anterior vitrectomy might be considered a safe and reliable solution for the anterior segment surgeon in managing vitreous prolapse during anterior segment surgeries.

Radiographic evidence of prominent retro and suborbicularis oculi fat in thyroid-associated orbitopathy.

PURPOSE: To compare the radiological differences in retro-orbicularis oculi fat (ROOF) and suborbiculars oculi fat (SOOF) among patients with thyroid-associated orbitopathy (TAO) and normal subjects using computed tomography (CT). METHODS: A retrospective analysis of orbital CTs was performed in 39 consecutive patients, who were imaged between October 2005 and June 2009. Bilateral orbital CTs of 16 patients with a final report significant for thyroid orbitopathy and 23 normal subjects were evaluated. All of the CTs consisted of 0.75 mm thick axial slices with 1.5 mm coronal reconstructions. Using the axial soft tissue windows, the ROOF and SOOF tissues were identified. The maximum ROOF thickness was measured perpendicular to the frontal bone, immediately superior to the supraorbital rim. Similarly, the maximum SOOF thickness was measured perpendicular to the zygomatic bone, immediately inferolateral to the infraorbital rim. The radiologist was blinded to the CT reports while conducting the measurements. Multivariable analysis of the two groups was then performed for comparison. RESULTS: Seventy-eight ROOF and SOOF measurements were obtained from 16 TAO patients with and 23 patients without TAO. The female-to-male ratio was 6:1 in the TAO group and only 3:2 among the normal subjects. The mean axial ROOF thicknesses was 3.8 ± 1.9 for TAO patients and 2.8 ± 1.0 mm in patients without TAO, while the SOOF thickness was 4.4 ± 1.0 and 3.4 ± 1.0 mm in the 2 groups, respectively. To account for bilateral measurements, the mixed model analysis was used. After controlling for age, gender, and ethnicity, the mean TAO ROOF and SOOF thicknesses were 1.0 mm (p = 0.04) and 0.9 mm (p < 0.01) greater than the control group, respectively. CONCLUSION: Retro-orbicularis oculi fat (ROOF) and suborbicularis oculi fat (SOOF) hypertrophy are two additional radiologic CT measurements that may be valuable in establishing the diagnosis of thyroid-associated orbitopathy.

Parental attitudes, values, and beliefs toward the return of results from exome sequencing in children.

Exome sequencing is being offered for children with undiagnosed conditions to identify a primary (causative) variant. Parental preferences for learning secondary (incidental) variants are largely unexplored. Our objective was to characterize values and beliefs that shape parents' preferences for learning their children's sequencing results. We conducted semi-structured interviews with 25 parents of 13 minor probands with a variety of rare genetic conditions. Parents were asked to discuss their preferences to receive four types of results from exome sequencing. Many parents preferred to receive all types of results. Parents had the most positive attitudes toward learning about variants that predispose to disorders treatable or preventable in childhood. They had reservations about learning about predispositions for untreatable adult-onset conditions and carrier status for recessive conditions. Parents described their success in coping with their child's condition as evidence for an ability to manage any additional negative health information. They felt responsible for learning about secondary variants, desiring a gain in control over their child's health. Our findings suggest that investigators should incorporate parents' perceptions of the value in receiving secondary variant information about their children when designing studies employing exome sequencing.

Hyperphagia among patients with Bardet-Biedl syndrome.

BACKGROUND: The importance of hyperphagia as a cause for energy imbalance in humans with Bardet-Biedl syndrome (BBS) has not been established. We therefore compared hyperphagic symptoms in patients with BBS vs. controls. METHODS: We studied 13 patients with BBS and 23 non-syndromic controls with similar age, sex and body mass index (BMI) z-score. A 13-item hyperphagia questionnaire was completed by patients' parents/guardians. RESULTS: Total hyperphagia questionnaire score was higher in BBS than controls (27.6 ± 9.0 vs. 19.1 ± 7.9, P = 0.005). Behaviour and drive subscales were higher for BBS than controls (12.5 ± 4.1 vs. 7.8 ± 3.2, P = 0.001, and 11.2 ± 4.1 vs. 8.3 ± 3.8, P = 0.04, respectively); severity was not significantly different between groups (3.8 ± 1.5 vs. 3.0 ± 1.3, P = 0.072). After adjustment for demographic variables and BMI z-score, total and behaviour subscale scores remained significantly different between groups, suggesting food-seeking activity, rather than preoccupation with food may be the main hyperphagic feature among patients with BBS. CONCLUSION: Appetite dysregulation may contribute to obesity in BBS.

Immunoproteomic analysis of potential serum biomarker candidates in human glaucoma.

PURPOSE: Evidence supporting the immune system involvement in glaucoma includes increased titers of serum antibodies to retina and optic nerve proteins, although their pathogenic importance remains unclear. This study using an antibody-based proteomics approach aimed to identify disease-related antigens as candidate biomarkers of glaucoma. METHODS: Serum samples were collected from 111 patients with primary open-angle glaucoma and an age-matched control group of 49 healthy subjects without glaucoma. For high-throughput characterization of antigens, serum IgG was eluted from five randomly selected glaucomatous samples and analyzed by linear ion trap mass spectrometry (LC-MS/MS). Serum titers of selected biomarker candidates were then measured by specific ELISAs in the whole sample pool (including an additional control group of diabetic retinopathy). RESULTS: LC-MS/MS analysis of IgG elutes revealed a complex panel of proteins, including those detectable only in glaucomatous samples. Interestingly, many of these antigens corresponded to upregulated retinal proteins previously identified in glaucomatous donors (or that exhibited increased methionine oxidation). Moreover, additional analysis detected a greater immunoreactivity of the patient sera to glaucomatous retinal proteins (or to oxidatively stressed cell culture proteins), thereby suggesting the importance of disease-related protein modifications in autoantibody production/reactivity. As a narrowing-down strategy for selection of initial biomarker candidates, we determined the serum proteins overlapping with the retinal proteins known to be up-regulated in glaucoma. Four of the selected 10 candidates (AIF, cyclic AMP-responsive element binding protein, ephrin type-A receptor, and huntingtin) exhibited higher ELISA titers in the glaucomatous sera. CONCLUSIONS: A number of serum proteins identified by this immunoproteomic study of human glaucoma may represent diseased tissue-related antigens and serve as candidate biomarkers of glaucoma.

Confocal microscopy of central toxic keratopathy.

PURPOSE: To examine the confocal microscopic findings in a case of late-onset central toxic keratopathy. METHODS: A 46-year-old man with central toxic keratopathy 2 months after IntraLASIK underwent confocal microscopy to examine the cellular findings within the flap interface. RESULTS: The confocal microscopy in central toxic keratopathy reveals activated keratocytes without aggregation of inflammatory cells. CONCLUSIONS: The lack of inflammatory cells in the interface is consistent with the noninflammatory nature of central toxic keratopathy. To our knowledge, this is the first report of confocal microscopy in presumed central toxic keratopathy.

Modified frontalis suspension technique with review of large series.

PURPOSE: To describe and report results of a modified frontalis suspension technique utilizing direct fixation to tarsus, lash margin rotation, eyelid crease fixation, conservative blepharoplasty, and rhomboidal configuration. METHODS: A retrospective chart review of frontalis suspension patients over a 28-year period was performed. RESULTS: Data from 171 eyelids in 93 patients were reviewed. Ages ranged from 1 to 84 years with a median age of 16. The indications for surgery included the following: congenital ptosis in 107 eyelids (62.6%), chronic progressive external ophthalmoplegia in 17 (9.9%), jaw winking ptosis in 14 (8.2%), blepharophimosis in 12 (7.0%), cranial nerve III palsy in 10 (5.8%), traumatic ptosis in 9 (5.3%), and myasthenia in 2 (1.2%). Autogenous fascia lata was utilized in 156 lids (91.3%), while silicone rods or banked fascia was used in 11 (6.4%) and 4 (2.3%) lids, respectively.Average follow up was 11.7 months (range 2 to 108 months). An excellent result was defined as ≤1 mm asymmetry in primary gaze and an eyelid position of 2.5 mm or less below the superior limbus. Eighty-nine of 93 patients (95.7%) achieved excellent results. Six lids in 4 patients (3.5%) were undercorrected. No patients were overcorrected. Only 2 patients with autogenous fascia lata (3.4%) required a secondary bilateral frontalis suspension at the 2- and 3-year time intervals. CONCLUSIONS: The authors believe that technique modifications including direct eyelid crease incision and tarsal fixation, conservative fat removal blepharoplasty even in children, lash margin rotation, and rhomboidal configuration with single midline brow incision give improved results of frontalis suspension when compared with conventional techniques.

Biomechanical effects of intraocular pressure elevation on optic nerve/lamina cribrosa before and after peripapillary scleral collagen cross-linking.

PURPOSE: To evaluate the biomechanical effect of intraocular pressure (IOP) elevation on the optic nerve/lamina cribrosa complex (ON/LC) and peripapillary sclera (PS) of porcine eyes before and after localized collagen cross-linking. METHODS: Eighteen porcine globes were divided evenly into three groups. The optic nerves were transected to expose the ON/LC, and each globe was infused through an in-line pressure transducer for direct IOP control. Surface wave velocity, a nondestructive measure of tissue stiffness, was measured across the ON/LC and PS before and after collagen cross-linking at IOPs of 10 and 30 mm Hg (groups 1 and 2) and at each globe's preinflation IOP and 80 mm Hg (group 3). In group 3, papillary strain was measured by analyzing the displacement of fiducial marks immediately adjacent to the ON/LC by using digital photography. Cross-linking in group 1 was achieved with riboflavin-ultraviolet A (UVA) delivery to the entire ON/LC and PS and, in groups 2 and 3, with an annular sponge soaked in glutaraldehyde (GTA) and applied only to the PS. RESULTS: Native PS was significantly stiffer than the ON/LC across all experiments. Before cross-linking, IOP elevation caused significant stiffening of both the ON/LC and PS. After cross-linking with either technique, IOP elevation stiffened the PS but not the ON/LC region. In group 3, papillary strain during IOP elevation was significantly reduced after PS cross-linking. CONCLUSIONS: Stiffening of the peripapillary scleral ring reduces the biomechanical sensitivity of the ON/LC complex to IOP elevation and may represent a novel mechanism for neuroprotection in glaucoma.

Rainbow glare as an optical side effect of IntraLASIK.

PURPOSE: To report a new optical side effect associated with the IntraLASIK procedure. DESIGN: Retrospective chart review and questionnaire of all patients treated with IntraLASIK from June 2004 to August 2005. PARTICIPANTS: A cohort of 585 eyes (312 patients) was divided sequentially into those treated with the older-model IntraLase laser (group 1: 399 eyes of 215 patients) and those treated with the newer model (group 2: 186 eyes of 97 patients). METHODS: Preoperative and postoperative refraction, visual acuity, pupillometry, pachymetry, intraocular pressure, mean topographic power and cylinder, wavefront aberrations, and answers to a questionnaire of symptoms were recorded. The precise spatial extent of the rainbow spectrum was drawn by select patients for calculation of the diffractive grating size responsible for the light scatter. A glass slide was also irradiated and photographed using the older model to simulate the rainbow spectrum. MAIN OUTCOME MEASURES: The symptom of rainbow glare was correlated with preoperative and postoperative factors and time between the most recent service call and surgery. RESULTS: In group 1, 90.2% of patients were successfully contacted, and 37 (69 eyes) reported symptoms of rainbow glare around lights, for an incidence of 19.07%. In group 2, 88.6% of patients were contacted, and 2 (4 eyes) reported similar symptoms, for an incidence of 2.32%. The odds ratio (OR) between the 2 groups is 9.4 (P<0.001). For every 10-mum increase in ablation depth, the OR is 1.2 (P = 0.038), and for every 30 days from the last service call, it is 1.5 (P = 0.007). The spatial extent of the color pattern was used to calculate the spacing array at approximately 9 mum, corresponding to the laser spot and line separation. CONCLUSIONS: Light scattering from the back surface of the IntraLASIK flap creates a spectral pattern whose visual impact is clinically inconsequential in the majority of patients. The spectral pattern and visual angle correspond to a grating size that matches the raster spot separation of IntraLase pulsing. Eyes treated with newer focusing optics of higher numerical aperture reduced the rainbow symptom. Variance in optical quality and numerical aperture can impact the spot size and uniformity of IntraLase flap creation.

Determination of activated protein C resistance in anticoagulated and lupus positive patients.

Clotting-based activated protein C (APC) assays have limitations when testing patients on oral anticoagulant (OA) therapy or with a lupus anticoagulant (LA). Predilution in factor V (FV)-deficient plasma and testing with phospholipid-rich Russell Viper venom (RVV)-based methods have been shown to be the most suitable methods when testing these patient groups, respectively. We evaluated a modified RVV based clotting test (Gradileiden V test; Gradipore, Sydney, Australia) in a large patient cohort and determined its sensitivity to the FV Leiden mutation. We also examined whether normal plasma can be used to dilute plasma from warfarinized patients without compromising sensitivity to the FV Leiden mutation. A total of 1,956 plasmas were studied including congenital protein C (five plasmas), and protein S deficiency (five plasmas), LA (29 plasmas), FV Leiden heterozygote (102 plasmas), and homozygote (five plasmas), warfarin (54 plasmas), standard heparin therapy (37 plasmas) and normal healthy controls (21 plasmas). Molecular analysis was performed on all samples. The effect of FV Leiden concentration on the APC ratio was examined by determining the APC resistance of a homozygous plasma serially diluted in six sources of normal plasma (NP). The relationship was non-linear and dependent on the initial APC ratio of the chosen source of NP. APC resistance was demonstrated in the varying sources of NP in dilutions of 1/4 (25% FV Leiden) to 1/32 (3% FV Leiden). A 1/2 dilution in pooled NP is recommended for patients on OA therapy because the test remains sensitive at levels of 25% FV Leiden and this is the dilution routinely used for other applications in a coagulation laboratory. The effect of a LA on the APC ratio was similarly studied by determining the APC resistance of a homozygous plasma serially diluted in two sources of LA-positive plasma. This relationship was also non-linear and dependent on the initial APC ratio of the LA-positive plasma. APC resistance was demonstrated in dilutions of 1/16 (6% FV Leiden) to 1/64 (1.5% FV Leiden) demonstrating the sensitivity of the test to APC resistance in the presence of a LA. Our results show the modified RVV-based test clearly predicts the presence of factor V Leiden in a large cohort of patients. The method offers advantages when testing patients with a LA and patients receiving warfarin providing a 1/2 predilution step in pooled NP is performed. Pooled NP does not affect the sensitivity of the test to the mutation, is routinely used in coagulation laboratories, and is considerably less expensive than FV-deficient plasma.

Failure to identify non-bovine reservoirs of Mycobacterium bovis in a region with a history of infected dairy-cattle herds.

The State of Texas had the most (cumulative) tuberculous cattle herds of any state in the United States during the decade ending in 1997. Of the cumulative 18 infected herds in Texas, 12 herds were concentrated in El Paso County (designated the 'El Paso milkshed'). To identify whether non-bovine reservoirs were a source of Mycobacterium bovis infection of cattle in this region, an investigation was conducted on the premises of 14 dairy herds (12 tuberculous and 2 non-affected herds) between May 1995 and June 1997. None of the 670 mammalian, avian and environmental (soil, water and air) samples collected and cultured from the premises of these herds was positive for the presence of M. bovis. None of the 119 human urine samples obtained from employees of these dairies was culture positive for M. bovis. Of 124 dairy-farm workers with tuberculin skin-test results, 48 showed positive test results. There was, however, no difference in percentages of positive skin-test results between farms without, and farms having, bovine tuberculosis within the last two years or longer. The percentage of positive reactions did not increase with length of time employed at a dairy with a history of confirmed tuberculosis. These findings suggest that non-bovine reservoirs appear not to be a factor responsible for tuberculosis of cattle in the El Paso milkshed.

Familial thrombophilia and the prothrombin 20210A mutation: association with increased thrombin generation and unusual thrombosis.

The 20210A prothrombin mutation has recently been associated with an increased risk of venous thrombosis, but the mechanism of the increased thrombotic risk in affected persons has not been elucidated. We report on a thrombophilic family in which the proband presented with cerebral vein thrombosis and homozygosity for the 20210A prothrombin mutation as her only identifiable risk factor for venous thrombosis. Extended genotyping of family members revealed seven other affected, but asymptomatic, first-degree relatives (one A/A homozygote and six G/A heterozygotes). Plasma levels of prothrombin, prothrombin fragments 1 + 2 and thrombin-antithrombin complexes were highest in A/A homozygotes, intermediate in G/A heterozygotes and lowest in those with the G/G homozygous normal genotype, while D-dimer levels were elevated only in A/A homozygotes. Our results suggest that the 20210A prothrombin mutation is associated with activation of coagulation and increased thrombin generation, not only in patients with a past history of thrombosis but also in otherwise healthy asymptomatic persons. In a similar fashion to the homozygous factor V Leiden mutation, patients with the homozygous 20210A prothrombin mutation could be at highest risk of thrombosis, as suggested by our patient who presented with unusual thrombosis.

Single or duplicate analysis for automated prothrombin time and activated partial thromboplastin time?

The introduction of automated coagulation analysers raises the possibility of performing routine coagulation tests as single rather than duplicate analyses. This study compares the duplicate results of the prothrombin time (PT) and activated partial thromboplastin time (aPTT) to that of a single result obtained by the MLA Electra 1000c using two different methods. The first method looks specifically at the difference between the mean duplicate result and the single result to determine if they alter patient management. This method found that two of 4152 PTs (0.048%) and two of 3047 aPTTs (0.065%) were clinically significant. The second method statistically assessed the agreement between the traditional mean duplicate result and the single test. This supported the introduction of single testing as the calculated 95% confidence intervals demonstrate that each result is interchangeable for purposes of clinical interpretation. These results supported the introduction of single testing for PT and aPTT estimation in our laboratory. The introduction of single testing was accompanied by changes to quality control and machine maintenance to ensure that the functions previously covered by duplicate testing were maintained. A strict protocol for repeat testing has also been adopted.