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Srikumaran D.,Wilmer Eye Institute | Munoz B.,Wilmer Eye Institute | Aldave A.J.,Jules Stein Eye Institute | Aquavella J.V.,Flaum Eye Institute | And 4 more authors.
Ophthalmology | Year: 2014

Design Retrospective, multicenter case series.ParticipantsA total of 158 eyes of 150 patients underwent KPro implantation at 5 participating tertiary centers in the United States between January 2003 and December 2006. Of those, 139 eyes of 133 patients were included in the analyses.Purpose To study the long-term outcomes of Boston type 1 keratoprosthesis (KPro) surgery.Methods The medical records of consecutive adult patients who received KPro surgery were reviewed. All patients with at least 1 postoperative visit were retained in the outcomes analyses. In eyes in which a repeat KPro procedure was performed, only the outcomes of the initial surgery were analyzed.Main Outcome Measures Visual acuity (VA) outcomes, postoperative complications, and device retention.Results The mean follow-up was 46.7±26 months with all but 4 eyes having at least 6 months of follow-up. Preoperatively, only 10.8% of the eyes had VA of ≥20/200. Postoperatively, the VA in 70% of eyes improved to ≥20/200. The probability of maintaining VA of ≥20/200 at 7 years was 50%. The device retention rate was estimated at 67% at 7 years. The 7-year cumulative incidence of complications was 49.7% for retroprosthetic membrane formation, 21.6% for glaucoma surgery, 18.6% for retinal detachment, and 15.5% for endophthalmitis.Conclusions Although the risk for complications with longer follow-up seemed to increase, this large multicenter cohort demonstrates favorable outcomes with KPro, with a large number of patients achieving and retaining useful vision over a 7-year period. © 2014 American Academy of Ophthalmology.

Khurana R.N.,2485 Hospital Drive | Khurana R.N.,University of California at San Francisco | Appa S.N.,Southern California Permanente Medical Group | McCannel C.A.,Jules Stein Eye Institute | And 5 more authors.
Ophthalmology | Year: 2014

Objective To describe the risk factors, clinical course, and complications of migration of a dexamethasone (DEX) intravitreal implant (OZURDEX; Allergan, Inc., Irvine, CA) into the anterior chamber and subsequent management strategies. Design Retrospective, observational case series. Participants Fifteen patients had 18 episodes of migration of the DEX implant into the anterior chamber. Methods The medical records of 15 patients with spontaneous migration of a DEX implant were retrospectively reviewed. Main Outcome Measures Migration of the DEX implant into the anterior chamber. Results Migration of a DEX intravitreal implant into the anterior chamber occurred in 6 patients who were aphakic, 4 patients with an anterior chamber intraocular lens, 2 patients with a scleral-fixated posterior chamber intraocular lens (PCIOL), 2 patients with a PCIOL, and 1 patient with an iris-fixated PCIOL. All 15 patients had prior pars plana vitrectomy, and 14 patients (93%) had no lens capsule. The average interval from DEX implant injection to detection of the implant migration into the anterior chamber was 13 days (range, 5-44 days). In 14 patients, corneal edema developed. Among those eyes undergoing surgical removal of the implant, earlier intervention reduced the likelihood of permanent corneal edema (0.5 days [from diagnosis of migration to surgical removal of the implant] vs. 5.5 days; P = 0.04). Aspiration was necessary to remove the implant in 6 patients. Among the 14 patients with corneal edema, the corneal edema did not resolve in 10 patients (71%), 6 (43%) of whom required corneal transplantation. Conclusions Absence of lens capsule and prior vitrectomy are risk factors for migration of the DEX implant into the anterior chamber. Early removal of the implant may be necessary to minimize the risk of chronic corneal edema. © 2014 by the American Academy of Ophthalmology.

Gorin M.B.,University of California at Los Angeles | Gorin M.B.,Jules Stein Eye Institute
Molecular Aspects of Medicine | Year: 2012

Age-related macular degeneration (AMD) is a common condition among the elderly population that leads to the progressive central vision loss and serious compromise of quality of life for its sufferers. It is also one of the few disorders for whom the investigation of its genetics has yielded rich insights into its diversity and causality and holds the promise of enabling clinicians to provide better risk assessments for individuals as well as to develop and selectively deploy new therapeutics to either prevent or slow the development of disease and lessen the threat of vision loss. The genetics of AMD began initially with the appreciation of familial aggregation and increase risk and expanded with the initial association of APOE variants with the disease. The first major breakthroughs came with family-based linkage studies of affected (and discordant) sibs, which identified a number of genetic loci and led to the targeted search of the 1q31 and 10q26 loci for associated variants. Three of the initial four reports for the CFH variant, Y402H, were based on regional candidate searches, as were the two initial reports of the ARMS2/HTRA1 locus variants. Case-control association studies initially also played a role in discovering the major genetic variants for AMD, and the success of those early studies have been used to fuel enthusiasm for the methodology for a number of diseases. Until 2010, all of the subsequent genetic variants associated with AMD came from candidate gene testing based on the complement factor pathway. In 2010, several large-scale genome-wide association studies (GWAS) identified genes that had not been previously identified. Much of this historical information is available in a number of recent reviews (Chen et al.; 2010b; Deangelis et al.; 2011; Fafowora and Gorin, 2012b; Francis and Klein, 2011; Kokotas et al.; 2011). Large meta analysis of AMD GWAS has added new loci and variants to this collection (Chen et al.; 2010a; Kopplin et al.; 2010; Yu et al.; 2011). This paper will focus on the ongoing controversies that are confronting AMD genetics at this time, rather than attempting to summarize this field, which has exploded in the past 5 years. © 2012 Elsevier Ltd. All rights reserved.

Mccannel C.A.,Jules Stein Eye Institute | Mccannel C.A.,University of California at Los Angeles | Reed D.C.,Jules Stein Eye Institute | Goldman D.R.,Jules Stein Eye Institute
Ophthalmology | Year: 2013

Purpose: To assess the effect of a Capsulorhexis Intensive Training Curriculum (CITC) on the rates of errant, continuous, curvilinear capsulorhexes (CCCs) during cataract surgery among resident surgeons at a teaching hospital. Design: Retrospective educational interventional case series. Participants and Controls: A total of 1037 consecutive cataract surgeries performed at Harbor-UCLA Medical Center during 4 consecutive academic years were considered. The baseline cohort consists of 434 cataract surgeries performed during the 2 academic years before the intervention. The postintervention cohort consists of 603 cataract surgeries performed during the following 2 consecutive academic years. Intervention: The principal intervention was the introduction of the CITC for residents on the Eyesi (VRmagic, Mannheim, Germany) ophthalmic virtual reality surgical simulator. Main Outcome Measures: The main outcome measure was the rate of errant CCCs among the capsulorhexes performed during resident surgical cases. Errant CCCs were defined as attempted CCCs that resulted in the attending physician taking over, radialization of the CCC, conversion to can-opener capsulorhexis, or any combination of the 3 aforementioned conditions. Secondary measures included the use of trypan blue during CCC and correlating errant CCC and surgeons' level of training (postgraduate year [PGY]). Results: There were 68 errant CCCs (15.7%) in the baseline cohort and 30 errant CCCs (5.0%; P < 0.0001) in the postintervention cohort, a 3.2-fold or 68% reduction. The use of trypan blue increased from 55.3% in the baseline cohort to 76.0% in the postintervention cohort (P < 0.00001), but within each cohort there was no significant difference in the rate of errant CCCs whether trypan blue was used or not. In the baseline cohort, there was a statistical trend toward fewer errant CCCs among PGY 4 (14.6%) compared with PGY 3 (22.8%) surgeons (P = 0.12). The postintervention cohort showed no significant difference in errant CCC rates between PGY 3 (4.4%) and PGY 4 (5.1%) surgeons (P = 1.00). Conclusions: This study strongly suggests that virtual reality surgical simulation training with the CITC on the Eyesi reduces the rate of errant capsulorhexes. The incorporation of a formal program for surgical training via virtual reality simulation should be strongly considered in ophthalmology resident surgical education to reduce the unnecessary risk of complications for live patients. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2013 by the American Academy of Ophthalmology Published by Elsevier Inc.

Caprioli J.,Jules Stein Eye Institute | Varma R.,Doheny Eye Institute
American Journal of Ophthalmology | Year: 2011

Purpose: To review the role of intervisit intraocular pressure (IOP) fluctuation as an independent risk factor for glaucoma. Design: Perspective after literature review. Methods: Analysis of pertinent publications in the peer-reviewed literature. Results: Disparate findings regarding the role of intervisit IOP variation have been published. IOP variation was a significant risk factor in the Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma Treatment Study, and other smaller studies. These studies have in common low IOPs (often after surgery) and moderately advanced disease. In the AGIS, when patients were stratified by mean IOP, only those patients with low IOPs showed the detrimental effects of IOP variation. IOP variation was not a significant risk factor in the Early Manifest Glaucoma Treatment Trial, and in 2 separate studies of ocular hypertensives. These studies have in common generally higher IOPs and an earlier stage of glaucoma (or no glaucoma at all). We believe these results are complementary rather than contradictory: existing data suggest that the effects of IOP variation depend on the characteristics of the patient, the baseline IOP, their stage of damage, the type of glaucoma, and other as-yet unknown factors. Conclusions: Practitioners should consider whether patients who are progressing at low mean IOP may benefit from having IOP variation reduced. Single elevated measures of IOP may not be an anomaly or may not be related to compliance, but may identify patients who are at high risk for progressive glaucomatous damage, and thus should be monitored more carefully and potentially treated more aggressively. © 2011 Elsevier Inc.

Matynia A.,Jules Stein Eye Institute
Experimental eye research | Year: 2012

Photoallodynia (photophobia) occurs when normal levels of light cause pain ranging from uncomfortable to debilitating. The only current treatment for photoallodynia is light avoidance. The first step to understanding the mechanisms of photoallodynia is to develop reliable animal behavioral tests of light aversion and identify the photoreceptors required to initiate this response. A reliable light/dark box behavioral assay was developed that measures light aversion independently from anxiety, allowing direct testing of one endophenotype of photoallodynia in mice. Mice lacking intrinsically photosensitive retinal ganglion cells (ipRGCs) exhibit reduced aversion to bright light, suggesting these cells are the primary circuit for light aversion. Mice treated with exogenous μ opiate receptor agonists exhibited dramatically enhanced light aversion, which was not dependent on ipRGCs, suggesting an alternative pathway for light is engaged. Morphine enhances retinal electrophysiological responses to light but only at low levels. This suggests that for the dramatic light aversion observed, opiates also sensitize central brain regions of photoallodynia. Taken together, our results suggest that light aversion has at least two dissociable mechanisms by which light causes specific allodynia behaviors: a primary ipRGC-based circuit, and a secondary ipRGC-independent circuit that is unmasked by morphine sensitization. These models will be useful in delineating upstream light sensory pathways and downstream avoidance pathways that apply to photoallodynia. Published by Elsevier Ltd.

Sun H.,Jules Stein Eye Institute
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2012

The eye is the human organ most sensitive to vitamin A deficiency because of vision's absolute and heavy dependence on vitamin A for light perception. Studies of the molecular basis of vision have provided important insights into the intricate mechanistic details of the function, transport and recycling of vitamin A and its derivatives (retinoid). This review focuses on retinoid-related membrane receptors and transporters. Three kinds of mammalian membrane receptors and transporters are discussed: opsins, best known as vitamin A-based light sensors in vision; ABCA4, an ATP-dependent transporter specializes in the transport of vitamin A derivative; and STRA6, a recently identified membrane receptor that mediates cellular uptake of vitamin A. The evolutionary driving forces for their existence and the wide spectrum of human diseases associated with these proteins are discussed. Lessons learned from the study of the visual system might be useful for understanding retinoid biology and retinoid-related diseases in other organ systems as well. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism. © 2011 Elsevier B.V.

Aldave A.J.,Jules Stein Eye Institute | Chen J.L.,Jules Stein Eye Institute | Zaman A.S.,Jules Stein Eye Institute | Deng S.X.,Jules Stein Eye Institute | Yu F.,Jules Stein Eye Institute
Cornea | Year: 2014

PURPOSE:: The aim of this study was to determine the outcomes after Descemet stripping endothelial keratoplasty (DSEK) in eyes with previous glaucoma surgery. METHODS:: This is a retrospective review of all DSEK procedures performed by 2 surgeons from May 1, 2006, to December 31, 2012. RESULTS:: Four hundred sixty-two DSEK procedures were performed, of which 113 (24%) were performed in 101 eyes after a trabeculectomy (52 procedures) and/or tube shunt implantation (76 procedures) (15 procedures in eyes with both). Primary graft failure and donor dislocation developed in 4.4% and 14.2% of cases in eyes with previous glaucoma surgery, not significantly different from the 3.2% (P = 0.56) and 11.5% (P = 0.51) in eyes without prior glaucoma surgery. During a mean follow-up of 20.7 ± 17.6 months, endothelial rejection developed in a greater percentage of eyes with previous glaucoma surgery (12.9%; 0.069/eye-year) compared with that in eyes without surgery (6.9%; 0.042/eye-year), although the difference was not statistically significant (P = 0.066 for percentage of eyes; P = 0.16 for rejection rate). Secondary graft failure developed in a significantly higher percentage of eyes with previous glaucoma surgery (15.9%; 0.094/eye-year) compared with that in eyes without surgery (3.2%; 0.019/eye-year) (P < 0.0001; P < 0.0001). Elevated intraocular pressure after DSEK was significantly more common in eyes with medically treated glaucoma (41.3%; 0.345/eye year) than in eyes with a previous glaucoma surgery (23.8%; 0.145/eye-year) and without glaucoma (20.0%; 0.138/eye year) (P = 0.009; P = 0.007). CONCLUSIONS:: Although intraoperative and early postoperative complications such as donor dislocation and primary graft failure are not significantly more common after DSEK in eyes with previous glaucoma surgery, secondary graft failure is. In contrast, other postoperative complications such as elevated intraocular pressure are significantly more common in eyes with medically treated glaucoma than in eyes with previous glaucoma surgery and without glaucoma. Copyright © 2014 by Lippincott Williams & Wilkins.

Rootman D.B.,Jules Stein Eye Institute
Ophthalmic Plastic and Reconstructive Surgery | Year: 2016

INTRODUCTION:: Surgical rehabilitation of thyroid orbitopathy involves reducing proptosis, treating strabismus, lengthening the eyelids, and managing aesthetic changes. Not all are necessary in each patient; however, they often are. The current investigation intends to describe postdecompression changes that may influence the staging of these procedures. METHODS:: In this retrospective cohort study, records of 169 patients who underwent orbital decompression between 1983 and 2001 were reviewed. A single orbital specialist confirmed all measurements. Time to follow up was defined as the most recent follow up after decompression and prior to any secondary procedures. No strabismus or eyelid surgery was performed at the time of decompression. Strabismus was measured with alternating prism cover test. Ductions were estimated utilizing Hirschberg’s method. Exophthalmometry was measured with Hertel. Eyelid positions were defined relative to the pupillary light reflex. Strabismus data were analyzed within eye pairs. Ductions, exophthalmometry and eyelid position were analyzed for each eye. T-test for paired data was utilized to compare means pre- and postoperatively. RESULTS:: The study population was on average 45 years old and 73.4% women. Average length of follow up was 1.2 years. Esotropia was significantly increased after decompression by an average of 8.1 prism diopters (p < 0.01). Exotropia and vertical deviations were not significantly altered. Ductions decreased by >5 degrees in at least one meridian for 68.1% of the population. Upper eyelid retraction remained unchanged; however, lower eyelid retraction improved by 50% from 1.4 mm to 0.7 mm (p < 0.01). Exophthalmometry improved from 23.5 mm to 19.7 mm (p < 0.01), and this result was correlated with the number of walls removed (Pearson r = −0.302, p < 0.01). CONCLUSIONS:: On average, esotropia and ductions tend to worsen with decompression surgery. This result supports the clinical dictum to avoid strabismus surgery until after decompression. The improvement in lower eyelid retraction suggests that at least lower eyelid-lengthening surgery should be reserved for after decompression, as there may be significant spontaneous improvement, while the same may not be true for upper eyelid retraction, which does not tend to change with decompression. © 2016 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Bitrian E.,Jules Stein Eye Institute | Caprioli J.,Jules Stein Eye Institute
American Journal of Ophthalmology | Year: 2010

Purpose: To report a surgical technique for aqueous misdirection refractory to medical treatment consisting of combined pars plana vitrectomy, hyaloido-zonulectomy, and peripheral iridectomy. Design: Noncomparative case series. Methods: The charts of 5 pseudophakic patients who sought treatment for aqueous humor misdirection refractory to medical treatment from May 2008 trough February 2009 were reviewed. All 5 patients underwent anterior vitrectomy, hyaloido-zonulectomy, and peripheral iridectomy with an anterior vitrector through a pars plana incision. Main outcome measures were preoperative and postoperative visual acuity, intraocular pressure, medications, slit-lamp examination results, and fundus findings. Results: Five female patients (age range, 23 to 89 years) had increased intraocular pressure and shallowing of the anterior chamber after cataract extraction or trabeculectomy, and none responded to conventional medical therapy. After surgery, prompt resolution of the aqueous misdirection was achieved in all cases. The follow-up was 7.6 months (range, 1 to 13 months). Conclusions: Aqueous misdirection refractory to medical treatment can be treated successfully with surgery consisting of partial pars plana vitrectomy, hyaloido-zonulectomy, and peripheral iridectomy. © 2010 Elsevier Inc. All rights reserved.

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