Although adjustable sutures are considered a standard technique in adult strabismus surgery, most surgeons are hesitant to attempt the technique in children, who are believed to be unlikely to cooperate for postoperative assessment and adjustment. Interest in using adjustable sutures in pediatric patients has increased with the development of surgical techniques specific to infants and children. This workshop briefly reviews the literature supporting the use of adjustable sutures in children and presents the approaches currently used by three experienced strabismus surgeons.
PURPOSE. Uveal melanoma (UM) is fatal in up to 50% of patients because of liver metastases, that are refractory to therapies currently available. While murine xenograft models for human uveal melanoma are available, they have limited utility for screening large compound libraries in drug discovery studies. Therefore, new robust preclinical models are needed that can efficiently evaluate drug efficacy for treatment of this malignancy. METHODS. UM cell lines generated from primary tumors (92.1, Mel270) and metastases (OMM2.3, OMM2.5, OMM1) were injected into the yolk of two-day-old zebrafish embryos. After six days, proliferation and active migration was quantified via automated confocal image analysis. To determine the suitability of this xenotransplantation model for drug testing, drugs with three different activities (Dasatinib, Quisinostat and MLN-4924) were added to the water of uveal melanoma-engrafted embryos. RESULTS. All tested UM cell lines proliferated and migrated in the embryos; significant differences could be discerned between cell lines: cells derived from metastases showed more migration and proliferation than cells derived from the primary tumors, and provided preclinical models for drug testing. Addition of the Src-inhibitor Dasatinib in the water of engrafted embryos reduced proliferation and migration of high Src-expressing 92.1 cells, but did not affect low Src-expressing metastatic OMM2.3 cells. Two experimental anticancer drugs, Quisinostat (a histone deacetylase inhibitor) and MLN-4924 (neddylation pathway inhibitor), blocked migration and proliferation of 92.1 and OMM2.3. CONCLUSIONS. We established a zebrafish xenograft model of human uveal melanoma with demonstrated applicability for screening large libraries of compounds in drug discovery studies.
Mutations in the ubiquitously expressed pre-mRNA processing factors 3, 8, and 31 (PRPF3, PRPF8, and PRPF31) cause nonsyndromic dominant retinitis pigmentosa in humans, an inherited retinal degeneration. It is unclear what mechanisms, or which cell types of the retina, are affected. Transgenic mice with the human mutations in these genes display late-onset morphological changes in the retinal pigment epithelium (RPE). To determine whether the observed morphological changes are preceded by abnormal RPE function, we investigated its phagocytic function in Prpf3(T494M/T494M), Prpf8(H2309P/H2309P), and Prpf31(+/-) mice. We observe decreased phagocytosis in primary RPE cultures from mutant mice, and this is replicated by shRNA-mediated knockdown of PRPF31 in human ARPE-19 cells. The diurnal rhythmicity of phagocytosis is almost lost, indicated by the marked attenuation of the phagocytic burst 2 hours after light onset. The strength of adhesion between RPE apical microvilli and photoreceptor outer segments also declined during peak adhesion in all mutants. In all models, at least one of the receptors involved in binding and internalization of shed photoreceptor outer segments was subjected to changes in localization. Although the mechanism underlying these changes in RPE function is yet to be elucidated, these data are consistent with the mouse RPE being the primary cell affected by mutations in the RNA splicing factors, and these changes occur at an early age.
PURPOSE: To assess whether brimonidine 0.15% alters retinal vascular autoregulation and short-term visual function in normal tension glaucoma patients who demonstrate retinal vascular dysregulation. DESIGN: Nonrandomized clinical trial. METHODS: In this prospective study, 46 normal tension glaucoma patients not previously treated with brimonidine underwent retinal vascular autoregulation testing and visual function assessment using frequency doubling technology perimetry and equivalent noise motion sensitivity testing. We measured blood flow in a major temporal retinal artery with subjects seated and then while reclined for 30 minutes. Patients having a change in retinal blood flow with posture change outside the range previously found in healthy subjects were classified as having retinal vascular dysregulation. They were treated with brimonidine 0.15% for 8 weeks and designated for retesting. RESULTS: Twenty-three patients demonstrated retinal vascular dysregulation at the initial visit. Younger age (P = .050) and diabetes (P = .055) were marginally significant risk factors for retinal vascular dysregulation. After the 8-week course with brimonidine, 14 of the 17 patients who completed the study showed a return of posture-induced retinal blood flow changes to levels consistent with normal retinal vascular autoregulation (P < .0001). We found no significant changes in frequency doubling technology perimetry or in motion detection parameters following treatment with brimondine (P > .09 for all tests performed). CONCLUSIONS: Brimonidine significantly improved impaired retinal vascular autoregulation in normal tension glaucoma patients, but short-term alteration in visual function could not be demonstrated.
PURPOSE: The purpose of this study was to determine whether a localized full-thickness eyelid excision results in a proportional decrease in the total number of eyelashes or whether a full complement of visible lashes persists, thus suggesting a compensatory increase in the anagen/telogen ratio among the remaining follicles. METHODS: A retrospective chart review was performed on 38 patients who underwent full-thickness eyelid resections repaired with primary eyelid closure for either benign or malignant eyelid lesions. Demographic and surgical data were collected, postoperative eyelid photographs were reviewed, and eyelashes were counted. RESULTS: There were 10 upper eyelids and 28 lower eyelids in 10 men and 28 women, with an average age of 57.9 years (range, 14-86 years). The lesion pathology was benign in 21 cases (55%) and malignant in 17 cases (45%). The full-thickness defect involved <25% of the eyelid in 16 cases (42%) and >25% of the eyelid in 22 cases (58%). The follow-up period ranged from 50 to 319 days, with an average of 94 days. In contralateral controls, upper eyelids had an average of 72.1 lashes and lower eyelids had an average of 38.2 lashes, and there was no statistical significance between men and women. In lower lids that underwent <25% resection, control lids had an average of 37.3 lashes and operative lids had 37.1 lashes. In lower lids that underwent >25% resection, control lids had an average of 38.7 lashes and operative lids had 34.2 lashes. This represents an 11.6% decrease and was statistically significant. In upper eyelids that underwent <25% resection and >25% resection, control eyelids had an average of 74.9 lashes and 69.3 lashes and operative eyelids had 77.6 lashes and 69.1 lashes, respectively. Finally, lash count was compared by benign versus malignant pathologic diagnosis. In upper eyelids with benign lesions and malignant lesions, control eyelids had an average of 73.8 lashes and 65.3 lashes and operative eyelids had 74.6 lashes and 68.3 lashes, respectively. In lower eyelids with benign pathology and malignant lesions, control eyelids had an average of 34.5 lashes and 41.4 lashes and operative eyelids had 33.8 lashes and 36.8 lashes. This represents an 11.1% decrease and was statistically significant. CONCLUSIONS: Full-thickness excision of eyelid margin tissue including lashes does not usually affect postoperative lash numbers. Because the total number of follicles is reduced, the percentage of lashes in the anagen versus the resting or telogen phase apparently increases compared with the preoperative state. This eyelash study contributes to the growing body of literature on the poorly understood topic of hair follicle cycle regulation.
PURPOSE: To report a novel surgical technique for lower eyelid involutional ectropion repair using a lateral tarsal strip and internal retractor reattachment procedure involving full-thickness eyelid sutures. METHODS:: A retrospective review was performed of patients who underwent repair of involutional ectropion via lateral tarsal strip and internal retractor reattachment with full-thickness eyelid sutures by 1 surgeon. Patients having concomitant or previous eyelid surgical procedures were excluded. Collected data included patient demographics, surgical outcomes, and length of follow up. RESULTS:: Forty-one lower eyelids of 31 patients with involutional ectropion underwent surgical repair. There were 17 men and 14 women in the age range of 69 to 92 years (mean age 82.2 ± 5.9 years). Surgical sites included 22 right and 19 left lower eyelids. Follow up ranged from 1 to 48 months with an average of 5.9 months. Surgical success with anatomical correction of involutional ectropion was achieved in 39 of 41 eyelids (95.1%). There were no perioperative or postoperative complications. Two of 41 (4.9%) eyelids had recurrence of ectropion 7 and 18 months after the procedure. CONCLUSIONS:: This procedure combining lateral tarsal strip with internal retractor reattachment involving full-thickness eyelid sutures effectively addresses horizontal eyelid laxity and tarsal instability, providing an effective technique to correct involutional ectropion of the lower eyelid.
Gharahkhani P, Burdon KP, Fogarty R, Sharma S, Hewitt AW, Martin S, Law MH, Cremin K, Bailey JCN, Loomis SJ, Pasquale LR, Haines JL, Hauser MA, Viswanathan AC, McGuffin P, Topouzis F, Foster PJ, Graham SL, Casson RJ, Chehade M, White AJ, Zhou T, Souzeau E, Landers J, Fitzgerald JT, Klebe S, Ruddle JB, Goldberg I, Healey PR, Healey PR, Healey PR, Mills RA, Wang JJ, Montgomery GW, Martin NG, Radford-Smith G, Whiteman DC, Brown MA, Wiggs JL, Mackey DA, Mitchell P, Macgregor S, Craig JE. Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma. Nat Genet 2014;46(10):1120-5.Abstract
Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 × 10(-19)), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10(-10)) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10(-10)). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.
Silicone oil continues to be an important aid in retinal detachment surgery. We report a case in which disparate responses to silicone oil were noted in the conjunctiva and intraocularly. Intraocularly, the oil permeated a fibrous membrane that formed behind a keratoprosthesis, the first example of this phenomenon. We detail the histological response to the oil at this site as well as a distinctly different reaction present to oil in the conjunctiva of the same eye. The divergence of histological responses provides a demonstration of the eye's apparent retained capacity to protect against intraocular inflammation, despite multiple previous surgeries.
Membrane-anchored mucins are present in the apical surface glycocalyx of mucosal epithelial cells, each mucosal epithelium having at least two of the mucins. The mucins have been ascribed barrier functions, but direct comparisons of their functions within the same epithelium have not been done. In an epithelial cell line that expresses the membrane-anchored mucins, MUC1 and MUC16, the mucins were independently and stably knocked down using shRNA. Barrier functions tested included dye penetrance, bacterial adherence and invasion, transepithelial resistance, tight junction formation, and apical surface size. Knockdown of MUC16 decreased all barrier functions tested, causing increased dye penetrance and bacterial invasion, decreased transepithelial resistance, surprisingly, disruption of tight junctions, and greater apical surface cell area. Knockdown of MUC1 did not decrease barrier function, in fact, barrier to dye penetrance and bacterial invasion increased significantly. These data suggest that barrier functions of membrane-anchored mucins vary in the context of other membrane mucins, and MUC16 provides a major barrier when present.
Dacryops of the lacrimal tissue can develop under diverse circumstances. Recent evidence suggests that scarring or obstruction of the lacrimal ducts may lead to their dilatation and formation of a cystic structure. Patients who undergo repeated orbital surgery may therefore be at greater risk of dacryops formation. In this report, a patient who underwent multiple corneal and glaucoma procedures including Boston type II keratoprosthesis, after acid burns to both eyes, is described. Over time, a fluid-filled collection developed in the lower orbit. On surgical exploration and incision, fluid was drained from a cystic lesion which abutted the lacrimal gland and spanned the upper and lower orbits. The lesion was removed and was proven by histopathology and immunohistochemistry to be dacryops. This is the first known case of dacryops associated with Boston type II keratoprosthesis.
Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a clinically heterogeneous maculopathy that may mimic other conditions and be difficult to diagnose. It is characterized by late onset, slow progression and high variability in morphologic and functional alterations. Diagnostic evaluation should include careful ophthalmoscopy and imaging studies. The typical ophthalmoscopic findings are bilateral, asymmetric, foveal or perifoveal, yellow, solitary, round to oval elevated subretinal lesions, often with central pigmentation. The lesions characteristically demonstrate increased autofluorescence and hypofluorescent lesions surrounded by irregular annular hyperfluorescence on fluorescein angiography. Optical coherence tomography studies demonstrate homogenous or heterogeneous hyperreflective material between the retinal pigment epithelium and the neurosensory retina. The visual prognosis is generally favorable, but visual loss can occur from chorioretinal atrophy and choroidal neovascularization.
The maintenance of mydriasis and the control of postoperative pain and inflammation are critical to the safety and success of cataract and intraocular lens replacement surgery. Appropriate mydriasis is usually achieved by topical and/or intracameral administration of anticholinergic agents, sympathomimetic agents, or both, with the most commonly used being cyclopentolate, tropicamide, and phenylephrine. Ocular inflammation is common after cataract surgery. Topical steroids and nonsteroidal anti-inflammatory drugs are widely used because they have been proved effective to control postsurgical inflammation and decrease pain. Topical nonsteroidal anti-inflammatory drugs have also been shown to help maintain dilation. However, use of multiple preoperative drops for pupil dilation, inflammation, and pain control have been shown to be time consuming, resulting in delays to the operating room, and they cause dissatisfaction among perioperative personnel; their use can also be associated with systemic side effects. Therefore, ophthalmologists have been in search of new options to streamline this process. This article will review the current medications commonly used for intraoperative mydriasis, as well as pain and inflammation control. In addition, a new combination of ketorolac, an anti-inflammatory agent, and phenylephrine, a mydriatic agent has recently been designed to maintain intraoperative mydriasis and to reduce postoperative pain and irritation from intraocular lens replacement surgery. Two Phase III clinical trials evaluating this combination have demonstrated statistically significant differences when compared to placebo in maintaining intraoperative mydriasis (P<0.00001) and in reducing pain in the early postoperative period (P=0.0002). This medication may be of benefit for use in cataract and lens replacement surgery in the near future.
Intermittent Horner syndrome is uncommon in both the adult and pediatric population. We describe a case of a pediatric patient with an intermittent Horner syndrome. Infrared photography and videography were used to help establish the diagnosis.
PURPOSE: To evaluate scotopic retinal organization in retinopathy of prematurity (ROP) through a study of spatial summation. METHODS: Thresholds for a range of stimulus diameters (0.4°-10°) were measured using a two alternative, spatial, forced choice psychophysical procedure. The critical diameter (DCRIT) for complete summation was estimated in subjects with a history of severe ROP (N = 7) and mild ROP (N = 17). Subjects who were born preterm and never had ROP (N = 16) and term-born subjects (N = 7) were also tested. The subjects ranged in age from 9 to 17 (median 13.5) years. RESULTS: Critical diameter for complete spatial summation was significantly larger in ROP subjects than in subjects who never had ROP and in term-born control subjects. Critical diameter varied significantly with severity of ROP. CONCLUSIONS: The larger DCRIT values in ROP are consistent with altered organization of the post receptor retina. This may offer the ROP retina a strategy for achieving noise reduction and good dark-adapted visual sensitivity.
The receptive fields of early visual neurons are anchored in retinotopic coordinates (Hubel and Wiesel, 1962). Eye movements shift these receptive fields and therefore require that different populations of neurons encode an object's constituent features across saccades. Whether feature groupings are preserved across successive fixations or processing starts anew with each fixation has been hotly debated (Melcher and Morrone, 2003; Melcher, 2005, 2010; Knapen et al., 2009; Cavanagh et al., 2010a,b; Morris et al., 2010). Here we show that feature integration initially occurs within retinotopic coordinates, but is then conserved within a spatiotopic coordinate frame independent of where the features fall on the retinas. With human observers, we first found that the relative timing of visual features plays a critical role in determining the spatial area over which features are grouped. We exploited this temporal dependence of feature integration to show that features co-occurring within 45 ms remain grouped across eye movements. Our results thus challenge purely feedforward models of feature integration (Pelli, 2008; Freeman and Simoncelli, 2011) that begin de novo after every eye movement, and implicate the involvement of brain areas beyond early visual cortex. The strong temporal dependence we quantify and its link with trans-saccadic object perception instead suggest that feature integration depends, at least in part, on feedback from higher brain areas (Mumford, 1992; Rao and Ballard, 1999; Di Lollo et al., 2000; Moore and Armstrong, 2003; Stanford et al., 2010).