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Item The Relationship of Age and Other Baseline Factors to Outcome of Initial Surgery for Intermittent Exotropia(Elsevier, 2020-04) Repka, Michael X.; Chandler, Danielle L.; Holmes, Jonathan M.; Donahue, Sean P.; Hoover, Darren L.; Mohney, Brian G.; Phillips, Paul H.; Stout, Ann U.; Ticho, Benjamin H.; Wallace, David K.; Ophthalmology, School of MedicinePurpose: To determine whether age at surgery is associated with surgical outcome of intermittent exotropia (IXT) at 3 years. Design: Secondary analysis of pooled data from a randomized trial. Methods: A total of 197 children 3 to <11 years of age with basic-type IXT of 15-40 prism diopters (Δ) were randomly assigned to 1 of 2 surgical procedures for treatment of intermittent exotropia. Masked examinations were conducted every 6 months for 3 years. The primary outcome was suboptimal surgical outcome by 3 years, defined as constant or intermittent exotropia of ≥10 Δ at distance or near by simultaneous prism and cover test (SPCT); constant esotropia of ≥6 Δ at distance or near by SPCT; or decrease in near stereoacuity of ≥2 octaves, at any masked examination; or reoperation without meeting any of these criteria. Results: The cumulative probability of a suboptimal surgical outcome by 3 years was 28% (19 of 72) for children 3 to <5 years of age, compared with 50% (57 of 125) for children 5 to <11 years of age (adjusted hazard ratio = 2.05; 95% confidence interval = 1.16 to 3.60). No statistically significant associations were found between suboptimal outcome and other baseline factors (magnitude of deviation, control score, fixation preference, or near stereoacuity) (P values ≥ .20). Conclusions: This analysis suggests that in children with IXT, younger age at surgery (3 to <5 years) is associated with better surgical outcomes; however, further evidence from a randomized trial comparing immediate with delayed surgery is needed for confirmation.Item Management of Peripapillary Choroidal Neovascular Membrane in Patients with Idiopathic Intracranial Hypertension(Wolters Kluwer, 2019-12) Ozgonul, Cem; Moinuddin, Omar; Munie, Metasebia; Lee, Michael S.; Bhatti, M. Tariq; Landau, Klara; Van Stavern, Gregory P.; Mackay, Devin D.; Lebas, Maud; DeLott, Lindsey B.; Cornblath, Wayne T.; Besirli, Cagri G.; Ophthalmology, School of MedicineObjective: To report the clinical features and treatment outcomes of patients with peripapillary choroidal neovascular membrane (CNVM) secondary to idiopathic intracranial hypertension (IIH). Methods: Retrospective, multicenter chart review of patients diagnosed with peripapillary CNVM in the course of the treatment and follow-up of IIH. Results: Records were reviewed from 7 different institutions between 2006 and 2016. Ten patients (13 eyes) with a diagnosis of IIH and at least 3 months of follow-up developed CNVM. Three of the total 10 patients developed bilateral CNVM. The mean time from the diagnosis of IIH to CNVM diagnosis was 41 months. Mean follow-up period was 8 months after diagnosis of CNVM. All patients were treated with acetazolamide for IIH. Seven eyes were observed, and 6 eyes were given anti-vascular endothelial growth factor (anti-VEGF) injections, including bevacizumab, ranibizumab, and aflibercept. All CNVMs regressed with subretinal fibrosis, and visual acuity improved in most patients. Papilledema resolved in only 1 eye, while the other 12 eyes had persistent papilledema at last follow-up. Conclusions: Peripapillary CNVM, a rare complication of IIH, often resolves spontaneously with treatment of IIH. In vision-threatening and/or persistent cases, intravitreal anti-VEGF treatment may be a safe and effective therapeutic option.Item The utility and risks of therapeutic nanotechnology in the retina(Sage, 2021-03-22) Scheive, Melanie; Yazdani, Saeed; Hajrasouliha, Amir R.; Ophthalmology, School of MedicineThe clinical application of nanotechnology in medicine is promising for therapeutic, diagnostic, and surgical improvements in the near future. Nanotechnologies in nano-ophthalmology are in the early stages of application in clinical contexts, including ocular drug and gene delivery systems addressing eye disorders, particularly retinopathies. Retinal diseases are challenging to treat as current interventions, such as intravitreal injections, are limited by their invasive nature. This review examines nanotechnological approaches to retinal diseases in a clinical context. Nanotechnology has the potential to transform pharmacological and surgical interventions by overcoming limitations posed by the protective anatomical and physiological barriers that limit access to the retina. Preclinical research in the application of nanoparticles in diagnostics indicates that nanoparticles can enhance existing diagnostic and screening tools to detect diseases earlier and more easily and improve disease progression monitoring precision.Item Defective INPP5E distribution in NPHP1‐related Senior–Loken syndrome(Wiley, 2021-01) Ning, Ke; Song, Emilie; Sendayen, Brent E.; Prosseda, Philipp P.; Chang, Kun-Che; Ghaffarieh, Alireza; Alvarado, Jorge A.; Wang, Biao; Haider, Kathryn M.; Berbari, Nicolas F.; Hu, Yang; Sun, Yang; Ophthalmology, School of MedicineBackground: Senior-Loken syndrome is a rare genetic disorder that presents with nephronophthisis and retinal degeneration, leading to end-stage renal disease and progressive blindness. The most frequent cause of juvenile nephronophthisis is a mutation in the nephronophthisis type 1 (NPHP1) gene. NPHP1 encodes the protein nephrocystin-1, which functions at the transition zone (TZ) of primary cilia. Methods: We report a 9-year-old Senior-Loken syndrome boy with NPHP1 deletion, who presents with bilateral vision decrease and cystic renal disease. Renal function deteriorated to require bilateral nephrectomy and renal transplant. We performed immunohistochemistry, H&E staining, and electron microscopy on the renal sample to determine the subcellular distribution of ciliary proteins in the absence of NPHP1. Results: Immunohistochemistry and electron microscopy of the resected kidney showed disorganized cystic structures with loss of cilia in renal tubules. Phosphoinositides have been recently recognized as critical components of the ciliary membrane and immunostaining of kidney sections for phosphoinositide 5-phosphatase, INPP5E, showed loss of staining compared to healthy control. Ophthalmic examination showed decreased electroretinogram consistent with early retinal degeneration. Conclusion: The decreased expression of INPP5E specifically in the primary cilium, coupled with disorganized cilia morphology, suggests a novel role of NPHP1 that it is involved in regulating ciliary phosphoinositide composition in the ciliary membrane of renal tubular cells.Item Patient Perception of Physician Attire in a Military Ophthalmology Clinic(Cureus, 2021-01-04) Scheive, Melanie; Gillis, John, II.; Gillis, Sarah; Legault, Gary L.; Ophthalmology, School of MedicineThe purpose of this study is to investigate patient preferences of physician attire in an outpatient military ophthalmology clinic to determine how these preferences affect patients' perceptions of physician competence and their overall clinical experience. Materials and methods This study is a prospective survey administered to patients at the ophthalmology clinic at Brooke Army Medical Center. USA. Patients who were willing to participate in a volunteer survey were included in this study. Demographic information and survey questions were utilized in this study along with words and pictures for patients to select a preference in physician attire in the clinic setting (scrubs, military uniform, or civilian professional attire) and surgical setting (surgical cap or a surgical bouffant). The survey asks patients if physician attire impacts patient confidence in physician abilities (yes or no) and if surgeon attire impacts the likelihood of the patient taking the surgeon's advice (yes or no). Results The demographic distribution includes 57-77 years old participants (53%), females (61%), retirees (49%), and dependent spouses (40%). The racial distribution includes 46% - Caucasian, 20% - African American, 22% - Hispanic, 6 - % Asian, and 6% - other. Most patient appointment types were established follow-up (77%) with only 12% new and 11% walk-in. The survey results (N=308) indicate that most patients (64%) did not have a preference in physician clinical attire, while 22% preferred scrubs, 11% preferred military uniform, and 3% preferred civilian attire. Most patients (66%) did not have a preference for surgical headwear, while 27% preferred the surgical cap, and 7% preferred the surgical bouffant. Only 9% of the patients surveyed indicated that physician attire impacted their confidence in their physician's ability, and 12% reported that attire impacted the likelihood of taking advice. Conclusions Most patients in an outpatient military ophthalmology clinic do not have a preference for physician attire or surgical headwear when surveyed. The majority of patients did not feel physician attire impacted their perception of physician's ability or their likelihood of taking advice. When indicating a preference, patients tended to prefer scrubs to outpatient civilian attire or military attire and trended towards preferring surgical cap over surgical bouffant for headwear.Item Intravitreal sirolimus for persistent, exudative age-related macular degeneration: a Pilot Study(BMC, 2021-02-16) Minturn, Robert J.; Bracha, Peter; Klein, Margaret J.; Chhablani, Jay; Harless, Ashley M.; Maturi, Raj K.; Ophthalmology, School of MedicineBackground and objective: To evaluate the safety and efficacy of intravitreal sirolimus for persistent, exudative age-related macular degeneration (AMD). Methods: This institutional review board approved, registered (NCT02357342), prospective, subject-masked, single center, randomized controlled trial in subjects with persistent, exudative Age-related macular degeneration compared intravitreal sirolimus monotherapy (every 2 months) versus monthly anti-vascular endothelial growth factor (VEGF) over six months. Results: 20 subjects were randomized to each arm of the trial. Upon completion of the trial 20 patients were analyzed in the control (anti-vascular endothelial growth factor) group and 17 patients were analyzed in the treatment (sirolimus) group. On average, subjects had 33 previous anti-VEGF injections prior to entry. The primary end-point, mean central subfield thickness (CST), increased by 20 µm in the anti-vascular endothelial growth factor group and decreased by 40 µm in the sirolimus group (p = 0.03). Visual acuity outcomes were similar between groups. Serious ocular adverse events in the sirolimus group included one subject each with anterior uveitis, central retinal artery occlusion and subretinal hemorrhage. Conclusion: Monotherapy with intravitreal sirolimus for subjects with persistent, exudative age-related macular degeneration appears to have a limited positive anatomic benefit. The presence of adverse events in the experimental group merits further evaluation, potentially as an adjuvant therapy. Trial registration This trial was registered with the clinicaltrials.gov, NCT02357342, and was approved by the institutional review board at Advarra. Funding was provided by an investigator-initiated grant from Santen. Santen played no role in the design or implementation of this study.Item Visual acuity outcomes and anti-VEGF therapy intensity in diabetic macular oedema: a real-world analysis of 28 658 patient eyes(BMJ, 2021-02) Ciulla, Thomas A.; Pollack, John S.; Williams, David F.; Ophthalmology, School of MedicineBackground/aim: To assess visual acuity (VA) outcomes and antivascular endothelial growth factor (anti-VEGF) treatment intensity in diabetic macular oedema (DMO). Methods: Retrospective analysis was performed in treatment-naïve patients with DMO from 2013 to 2018 using a database of aggregated de-identified electronic medical records (Vestrum Health). Results: At 1 year, 28 658 patient eyes underwent a mean of 6.4 anti-VEGF injections, gaining a mean of +4.2 letters (95% confidence interval for mean gain: +4.0 to +4.5 letters, p<0.001). When stratified by anti-VEGF medication and by years 2013-2018, no clinically meaningful differences in injection frequency or 1-year VA change resulted. At 1 year, 50% of eyes received ≤6 injections, while <20% received 10-13 injections, representing monthly treatment. Mean letters gained at 1 year generally showed a linear relationship with mean number of anti-VEGF injections, beyond two injections. Eyes with good baseline VA (≥20/40) generally were at risk of VA loss at 1 year; those with moderately severe baseline impairment (20/70 to 20/200) who received ≥10 injections improved by a mean of +10.3 letters. Conclusion: In clinical practice, patients with DMO undergo fewer anti-VEGF injections and exhibit worse visual gains compared with patients in randomised clinical trials. Visual outcomes correlate with treatment intensity at 1 year, with ceiling effects related to baseline VA.Item Noninvasive Monitoring and Neurointerventional Management of Idiopathic Intracranial Hypertension(Thieme, 2020-04) Lang, Matthew; Mathew, Sunu; Harris, Alon; Tejada, Juan; Kovoor, Jerry M.; Ophthalmology, School of MedicineIdiopathic intracranial hypertension (IIH) is characterized by isolated rise in intracranial pressure (ICP) leading to chronic, debilitating headaches, tinnitus, and vision loss. Conventional diagnostics and monitoring primarily require the use of invasive procedure like lumbar puncture to measure ICP, while traditional management strategies involve weight reduction and medical treatment with acetazolamide. In an effort to reduce the need for invasive procedures, noninvasive methods of ICP monitoring such as optic nerve sheath diameter measurements and two-depth transcranial Doppler ultrasonography have been developed. In cases of refractory and fulminant IIH, surgical management strategies such as optic nerve sheath fenestration (ONSF), ventriculoperitoneal (VP) and lumboperitoneal (LP) shunting, and transverse venous sinus stenting are used to relieve symptoms via ICP reduction. While ONSF and VP/LP shunting exhibit utility primarily for the treatment of vision loss and headache, respectively, venous sinus stenting may prove to be an effective option in the management of all symptoms of IIH. Most importantly, consideration of the patient’s individual symptoms and values should be taken into account when choosing the optimal surgical management strategy for patients with IIH.Item Outcomes of Bilateral Cataract Surgery in Infants 7 to 24 Months of Age Using the Toddler Aphakia and Pseudophakia Treatment Study Registry(Elsevier, 2021-02) Bothun, Erick D.; Wilson, M. Edward; Vanderveen, Deborah K.; Plager, David A.; Freedman, Sharon F.; Trivedi, Rupal H.; Traboulsi, Elias I.; Anderson, Jill S.; Loh, Allison R.; Yen, Kimberly G.; Weil, Natalie C.; Morrison, David; Lambert, Scott R.; Ophthalmology, School of MedicinePurpose To evaluate outcomes of bilateral cataract surgery in children aged 7 to 24 months and compare rates of adverse events (AEs) with other Toddler Aphakia and Pseudophakia Study (TAPS) registry outcomes. Design Retrospective clinical study at 10 Infant Aphakia Treatment Study (IATS) sites. Statistical analyses comparing this cohort with previously reported TAPS registry cohorts. Participants Children enrolled in the TAPS registry between 2004 and 2010. Methods Children underwent bilateral cataract surgery with or without intraocular lens (IOL) placement at age 7 to 24 months with 5 years of postsurgical follow-up. Main Outcome Measures Visual acuity (VA), occurrence of strabismus, AEs, and reoperations. Results A total of 40 children (76 eyes) who underwent bilateral cataract surgery with primary posterior capsulectomy were identified with a median age at cataract surgery of 11 months (7–23); 68% received a primary IOL. Recurrent visual axis opacification (VAO) occurred in 7.5% and was associated only with the use of an IOL (odds ratio, 6.10; P = 0.005). Glaucoma suspect (GS) was diagnosed in 2.5%, but no child developed glaucoma. In this bilateral cohort, AEs (8/40, 20%), including glaucoma or GS and VAO, and reoperations occurred in a similar proportion to that of the published unilateral TAPS cohort. When analyzed with children aged 1 to 7 months at bilateral surgery, the incidence of AEs and glaucoma or GS correlated strongly with age at surgery (P = 0.011/0.004) and glaucoma correlated with microcornea (P = 0.040) but not with IOL insertion (P = 0.15). Conclusions Follow-up to age 5 years after bilateral cataract surgery in children aged 7 to 24 months reveals a low rate of VAO and very rare glaucoma or GS diagnosis compared with infants with cataracts operated at < 7 months of age despite primary IOL implantation in most children in the group aged 7 to 24 months. The use of an IOL increases the risk of VAO irrespective of age at surgery.Item Small molecule target identification using photo-affinity chromatography(Elsevier, 2019) Seo, Seung-Yong; Corson, Timothy W.; Ophthalmology, School of MedicineIdentification of the protein targets of bioactive small molecules is a routine challenge in chemical biology and phenotype-based drug discovery. Recent years have seen an explosion of approaches to meeting this challenge, but the traditional method of affinity pulldowns remains a practical choice in many contexts. This technique can be used as long as an affinity probe can be synthesized, usually with a crosslinking moiety to enable photo-affinity pulldowns. It can be applied to varied tissue types and can be performed with minimal specialized equipment. Here, we provide our protocol for photo-affinity pulldown experiments, with notes on making this method generally applicable to varied target identification challenges.