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Ung L, Wang Y, Vangel M, Davies EC, Gardiner M, Bispo PJM, Gilmore MS, Chodosh J. Validation of a Comprehensive Clinical Algorithm for the Assessment and Treatment of Microbial Keratitis. Am J Ophthalmol 2020;214:97-109.Abstract
PURPOSE: To validate a comprehensive clinical algorithm for the assessment and treatment of microbial keratitis (MK). DESIGN: Retrospective cohort study. METHODS: The "1, 2, 3 Rule" for the initial management of MK was conceived by Vital and associates in 2007 to inform the decision as to when to perform corneal cultures. The rule is invoked when any 1 of 3 clinical parameters is met: ≥1+ anterior chamber cells, ≥2 mm infiltrate, or infiltrate ≤3 mm distance from the corneal center. When the rule is met, we added the mandatory use of fortified topical antibiotics after cultures are obtained. We compared outcomes of cases presenting to Massachusetts Eye and Ear 2 years before (Group I, n = 665) and after (Group II, n = 767) algorithm implementation. The primary composite outcome was a vision-threatening complication, such as corneal perforation. RESULTS: At a median follow-up of 67.0 and 60.0 days, respectively, 172 patients experienced a vision-threatening complication (Group I, 12.9% vs Group II, 11.2%, P = .51). While the algorithm codified conventional management practice at either end of disease severity, the effect of algorithm-augmented care was best appreciated in patients with lesions satisfying only 1 criterion. In this group, there was an increase in the proportion of patients undergoing culture at presentation (54.6% vs 67.7%, P = .006), fortified antibiotic prescription (29.7% vs 53.9%, P < .001), and reduction in vision-threatening complications (9.7% vs 1.8%, P = .001). The proportion of patients who were not cultured at presentation but later required culturing decreased (13.4% vs 5.1%, P = .001), as did patients who did not meet any criteria but were nonetheless cultured (23.9% vs 8.5%, P < .001). Multiple logistic regression showed that all algorithm parameters were independently associated with outcome: ≥1+ anterior chamber cells (odds ratio [OR] 1.66, 95% confidence interval 1.09-2.52); ≥2 mm infiltrate (OR 4.74, 2.68-8.40); and ≤3 mm from corneal center (OR 2.82, 1.85-4.31), confirmed with comparison to a bootstrapped sample (n = 10,000). CONCLUSIONS: The implementation of this algorithm reduced vision-threatening complications for patients with lesions satisfying only 1 criterion, arguably the most difficult patients in whom to judge disease severity. Implementation also led to a decrease in patients receiving unnecessary care.
Soh YQ, Kocaba V, Weiss JS, Jurkunas UV, Kinoshita S, Aldave AJ, Mehta JS. Corneal dystrophies. Nat Rev Dis Primers 2020;6(1):46.Abstract
Corneal dystrophies are broadly defined as inherited disorders that affect any layer of the cornea and are usually progressive, bilateral conditions that do not have systemic effects. The 2015 International Classification of Corneal Dystrophies classifies corneal dystrophies into four classes: epithelial and subepithelial dystrophies, epithelial-stromal TGFBI dystrophies, stromal dystrophies and endothelial dystrophies. Whereas some corneal dystrophies may result in few or mild symptoms and morbidity throughout a patient's lifetime, others may progress and eventually result in substantial visual and ocular disturbances that require medical or surgical intervention. Corneal transplantation, either with full-thickness or partial-thickness donor tissue, may be indicated for patients with advanced corneal dystrophies. Although corneal transplantation techniques have improved considerably over the past two decades, these surgeries are still associated with postoperative risks of disease recurrence, graft failure and other complications that may result in blindness. In addition, a global shortage of cadaveric corneal graft tissue critically limits accessibility to corneal transplantation in some parts of the world. Ongoing advances in gene therapy, regenerative therapy and cell augmentation therapy may eventually result in the development of alternative, novel treatments for corneal dystrophies, which may substantially improve the quality of life of patients with these disorders.
Elhusseiny AM, Jamerson EC, Menshawey R, Tam EK, El Sayed YM. Collector Channels: Role and Evaluation in Schlemm's Canal Surgery. Curr Eye Res 2020;45(10):1181-1187.Abstract
OBJECTIVES: 1) To elucidate the role of collector channels in the aqueous humor outflow pathway 2) To suggest anatomic and functional methods of imaging collector channels in-vitro and in-vivo and 3) To discuss the role of such imaging modalities in the surgical management of glaucoma. METHODS: A thorough literature search was conducted on databases for studies published in English regarding the available methods to determine the role of collecting channels in normal and glaucomatous patients and to assess their patency. RESULTS: Intraocular pressure (IOP) exists as a balance between aqueous humor production and aqueous humor outflow. Collector channels are an essential anatomical constituent of the distal portion of the conventional aqueous humor outflow pathway. There are different surgical options for glaucoma management and with the recent advances in Schlemm's canal-based surgeries, collector channel's patency became a key factor in determining the optimum management for the glaucomatous eye. The advent of anatomic imaging methods has improved the ability to visualize collector channel morphology in-vitro, including swept-source optical coherence tomography (SS-OCT), spectral domain optical coherence tomography (SD-OCT), micro-computed tomography (micro CT), new immunohistochemistry techniques and scanning electron microscopy. The recent advent of real-time assessment of collector channel patency (including evaluation of episcleral venous outflow, observation of episcleral venous fluid wave, and tracer studies utilizing fluorescein, indocyanine green, and trypan blue) has been validated by the aforementioned anatomic imaging modalities. CONCLUSIONS: New modalities of in-vitro and in-vivo studies of collector channels provide promise to aid in the assessment of collector channel patency and individualization of surgical management for glaucoma patients.
Collett G, Elhusseiny AM, Scelfo C, Whitman MC, VanderVeen DK. Ocular injury via epinephrine auto-injector. J AAPOS 2020;Abstract
Intraocular injury by epinephrine auto-injector has been rarely reported. Toxic risk to the intraocular structures is suspected, but the evidence is inconclusive. We present the case of a 2-year-old girl who sustained an injury to her right eye by inadvertent epinephrine injection. Cataract surgery was performed to treat an increasingly opaque lens, and an intraocular lens was implanted. The visual outcome was good, with no retinal damage.
Cogné B, Latypova X, Senaratne LDS, Martin L, Koboldt DC, Kellaris G, Fievet L, Le Meur G, Caldari D, Debray D, Nizon M, Frengen E, Bowne SJ, Consortium L99, Cadena EL, Daiger SP, Bujakowska KM, Pierce EA, Gorin M, Katsanis N, Bézieau S, Petersen-Jones SM, Occelli LM, Lyons LA, Legeai-Mallet L, Sullivan LS, Davis EE, Isidor B. Mutations in the Kinesin-2 Motor KIF3B Cause an Autosomal-Dominant Ciliopathy. Am J Hum Genet 2020;106(6):893-904.Abstract
Kinesin-2 enables ciliary assembly and maintenance as an anterograde intraflagellar transport (IFT) motor. Molecular motor activity is driven by a heterotrimeric complex comprised of KIF3A and KIF3B or KIF3C plus one non-motor subunit, KIFAP3. Using exome sequencing, we identified heterozygous KIF3B variants in two unrelated families with hallmark ciliopathy phenotypes. In the first family, the proband presents with hepatic fibrosis, retinitis pigmentosa, and postaxial polydactyly; he harbors a de novo c.748G>C (p.Glu250Gln) variant affecting the kinesin motor domain encoded by KIF3B. The second family is a six-generation pedigree affected predominantly by retinitis pigmentosa. Affected individuals carry a heterozygous c.1568T>C (p.Leu523Pro) KIF3B variant segregating in an autosomal-dominant pattern. We observed a significant increase in primary cilia length in vitro in the context of either of the two mutations while variant KIF3B proteins retained stability indistinguishable from wild type. Furthermore, we tested the effects of KIF3B mutant mRNA expression in the developing zebrafish retina. In the presence of either missense variant, rhodopsin was sequestered to the photoreceptor rod inner segment layer with a concomitant increase in photoreceptor cilia length. Notably, impaired rhodopsin trafficking is also characteristic of recessive KIF3B models as exemplified by an early-onset, autosomal-recessive, progressive retinal degeneration in Bengal cats; we identified a c.1000G>A (p.Ala334Thr) KIF3B variant by genome-wide association study and whole-genome sequencing. Together, our genetic, cell-based, and in vivo modeling data delineate an autosomal-dominant syndromic retinal ciliopathy in humans and suggest that multiple KIF3B pathomechanisms can impair kinesin-driven ciliary transport in the photoreceptor.
Agarwal A, Agrawal R, Raje D, Testi I, Mahajan S, Gunasekeran DV, Aggarwal K, Murthy SI, Westcott M, Chee S-P, McCluskey P, Ho SL, Teoh S, Cimino L, Biswas J, Narain S, Agarwal M, Mahendradas P, Khairallah M, Jones N, Tugal-Tutkun I, Babu K, Basu S, Carreño E, Lee R, Al-Dhibi H, Bodaghi B, Invernizzi A, Goldstein DA, Herbort CP, Barisani-Asenbauer T, González-López JJ, Androudi S, Bansal R, Moharana B, Esposti SD, Tasiopoulou A, Nadarajah S, Agarwal M, Abraham S, Vala R, Singh R, Sharma A, Sharma K, Zierhut M, Kon OM, Cunningham ET, Kempen JH, Nguyen QD, Pavesio C, Gupta V. Twenty-four Month Outcomes in the Collaborative Ocular Tuberculosis Study (COTS)-1: Defining the "Cure" in Ocular Tuberculosis. Ocul Immunol Inflamm 2020;:1-9.Abstract
PURPOSE: To report the clinical findings, anatomical features, and treatment outcomes in subjects with ocular tuberculosis (OTB) at 24 months in the Collaborative Ocular Tuberculosis Study (COTS)-1. METHODS: Of the 945 subjects included in COTS-1, those who completed a 24-month follow-up after completion of treatment were included. The main outcome measure was a number of patients with treatment failure (TF). RESULTS: 228 subjects (120 males; mean age of 42.82 ± 14.73 years) were included. Most common phenotype of uveitis was posterior ( = 81; 35.53%), and panuveitis ( = 76; 33.33%). Fifty-two patients (22.81%) had TF. On univariable analysis, odds of high TF was observed with bilaterality (OR: 3.46, = .003), vitreous haze (OR: 2.14, = .018), and use of immunosuppressive therapies (OR: 5.45, = .003). However, only bilaterality was significant in the multiple regression model (OR: 2.84; = .02). CONCLUSIONS: Majority of subjects (>75%) achieved cure in the COTS-1 at 24-month follow-up. The concept of "cure" may be a valuable clinical endpoint in trials for OTB.
Valdes LM, Sobrin L. Uveitis Therapy: The Corticosteroid Options. Drugs 2020;80(8):765-773.Abstract
Uveitis is characterized by intraocular inflammation involving the uveal tract; its etiologies generally fall into two broad categories: autoimmune/inflammatory or infectious. Corticosteroids  are a powerful and important class of medications ubiquitous in the treatment of uveitis. They may be given systemically or locally, in the form of topical drops, periocular injection, intravitreal suspension, or intravitreal implant. This review describes each of the currently available corticosteroid treatment options for uveitis, including favorable and unfavorable characteristics of each as well as applicable clinical trials. The main advantage of corticosteroids as a whole is their ability to quickly and effectively control inflammation early on in the course of uveitis. However, they can have serious side effects, whether localized to the eye (such as cataract and elevated intraocular pressure) or systemic (such as osteonecrosis and adrenal insufficiency) and in the majority of cases of uveitis are not an appropriate option for long-term therapy.
Chen JJ, Flanagan EP, Bhatti TM, Jitprapaikulsan J, Dubey D, Lopez Chiriboga ASS, Fryer JP, Weinshenker BG, McKeon A, Tillema J-M, Lennon VA, Lucchinetti CF, Kunchok A, McClelland CM, Lee MS, Bennett JL, Pelak VS, Van Stavern G, Adesina O-OO, Eggenberger ER, Acierno MD, Wingerchuk DM, Lam BL, Moss H, Beres S, Gilbert AL, Shah V, Armstrong G, Heidary G, Cestari DM, Stiebel-Kalish H, Pittock SJ. Steroid-sparing maintenance immunotherapy for MOG-IgG associated disorder. Neurology 2020;95(2):e111-e120.Abstract
OBJECTIVE: Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) often manifests with recurrent CNS demyelinating attacks. The optimal treatment for reducing relapses is unknown. To help determine the efficacy of long-term immunotherapy in preventing relapse in patients with MOGAD, we conducted a multicenter retrospective study to determine the rate of relapses on various treatments. METHODS: We determined the frequency of relapses in patients receiving various forms of long-term immunotherapy for MOGAD. Inclusion criteria were history of ≥1 CNS demyelinating attacks, MOG-IgG seropositivity, and immunotherapy for ≥6 months. Patients were reviewed for CNS demyelinating attacks before and during long-term immunotherapy. RESULTS: Seventy patients were included. The median age at initial CNS demyelinating attack was 29 years (range 3-61 years; 33% <18 years), and 59% were female. The median annualized relapse rate (ARR) before treatment was 1.6. On maintenance immunotherapy, the proportion of patients with relapse was as follows: mycophenolate mofetil 74% (14 of 19; ARR 0.67), rituximab 61% (22 of 36; ARR 0.59), azathioprine 59% (13 of 22; ARR 0.2), and IV immunoglobulin (IVIG) 20% (2 of 10; ARR 0). The overall median ARR on these 4 treatments was 0.3. All 9 patients treated with multiple sclerosis (MS) disease-modifying agents had a breakthrough relapse on treatment (ARR 1.5). CONCLUSION: This large retrospective multicenter study of patients with MOGAD suggests that maintenance immunotherapy reduces recurrent CNS demyelinating attacks, with the lowest ARR being associated with maintenance IVIG therapy. Traditional MS disease-modifying agents appear to be ineffective. Prospective randomized controlled studies are required to validate these conclusions.
Chang MY, Binenbaum G, Heidary G, Morrison DG, Galvin JA, Trivedi RH, Pineles SL. Imaging Methods for Differentiating Pediatric Papilledema from Pseudopapilledema: A Report by the American Academy of Ophthalmology. Ophthalmology 2020;127(10):1416-1423.Abstract
PURPOSE: To review the published literature on the accuracy of ophthalmic imaging methods to differentiate between papilledema and pseudopapilledema in children. METHODS: Literature searches were conducted in January 2020 in the PubMed database for English-language studies with no date restrictions and in the Cochrane Library database without any restrictions. The combined searches yielded 354 abstracts, of which 17 were reviewed in full text. Six of these were considered appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. All 6 included studies were rated as level III evidence. RESULTS: Fluorescein angiography, a combination of 2 OCT protocols, and multicolor confocal scanning laser ophthalmoscopy (Spectralis SD-OCT; Heidelberg Engineering, Heidelberg, Germany) demonstrated the highest positive percent agreement (92%-100%; 95% confidence interval [CI], 69%-100%) and negative percent agreement (92%-100%; 95% CI, 70%-100%) with a clinical diagnosis of papilledema in children. However, results must be interpreted with caution owing to methodologic limitations, including a small sample size leading to wide CIs and an overall lack of data (there was only 1 study each for the above methods and protocols). Ultrasonographic measures showed either a high positive percent agreement (up to 95%) with low negative percent agreement (as low as 58%) or vice versa. Autofluorescence and fundus photography showed a lower positive (40%-60%) and negative (57%) percent agreement. CONCLUSIONS: Although several imaging methods demonstrated high positive and negative percent agreement with clinical diagnosis, no ophthalmic imaging method conclusively differentiated papilledema from pseudopapilledema in children because of the lack of high-quality evidence. Clinicians must continue to conduct thorough history-taking and examination and make judicious use of ancillary testing to determine which children warrant further workup for papilledema.
Jakobiec FA, Eagle RC, Selig M, Ma L, Shields C. Clinical Implications of Goblet Cells in Dacryoadenosis and Normal Human Lacrimal Glands. Am J Ophthalmol 2020;213:267-282.Abstract
PURPOSE: The purpose of this study was to investigate an enlarged dacryoadenotic lacrimal gland and normal lacrimal glands for the presence of goblet cells (mucocytes). DESIGN: Retrospective clinicopathologic series. METHODS: An enlarged lacrimal gland (dacryoadenosis) without obvious histopathologic alterations was extensively evaluated histochemically, immunohistochemically, and ultrastructurally to detect the presence of goblet cells and to compare the findings with those in five normal lacrimal glands. RESULTS: Granular, zymogen-rich pyramidal acinar cells in normal glands predominated over a previously not reported subpopulation of nongranular, pale-staining cells in both dacryoadenotic and normal lacrimal glands. These cells histochemically stained positively with mucicarmine and Alcian blue. Immunohistochemical and electron microscopic evaluations established that there was a displacement or replacement of cytoplasmic gross cystic disease fluid protein-15 and CK 7-positive tonofilaments in the pale acinar cells by myriad mucus granules. The goblet cells constituted approximately 2% of the normal acinar cells and 5% of dacryoadenotic acinar cells. A depletion of myoepithelial cells and ectopic intra-acinar ductular cells were also observed in dacryoadenosis. CONCLUSION: Dacryoadenosis is caused by an increase in the number of acini without individual acinar cell hyperplasia. A normal cytologic feature of the lacrimal gland is the presence of acinar goblet cells that had been long overlooked; they are increased in number in dacryoadenosis. Intra-acinar ductular cells and the scattered loss of myoepithelial cells are other abnormalities in dacryoadenosis. The presence of lacrimal gland goblet cells may have physiologic implications for the precorneal tear film and its derangements as well as for the histogenesis of mucus-producing carcinomas.
Sohn EH, Strohbehn A, Stryjewski T, Brodowska K, Flamme-Wiese MJ, Mullins RF, Eliott D. POSTERIORLY INSERTED VITREOUS BASE: Preoperative Characteristics, Intraoperative Findings, and Outcomes After Vitrectomy. Retina 2020;40(5):943-950.Abstract
PURPOSE: To determine the preoperative characteristics, intraoperative and postoperative complications, and outcomes of eyes with posteriorly inserted vitreous base. METHODS: In this retrospective, observational, consecutive case series at 2 academic centers, 37 patients were studied who had posteriorly inserted vitreous base noted during vitrectomy. Posteriorly inserted vitreous base was defined as the insertion of the posterior hyaloid membrane being located posterior to the vortex veins. Fifteen eyes were analyzed in a histopathologic study of donor eyes to determine the average distance of the ora serrata from the vortex veins as this distance is uncertain. RESULTS: Posteriorly inserted vitreous base was identified during vitrectomy in 31 eyes with rhegmatogenous retinal detachment (84%), 4 with macular hole (11%), 1 with vitreous hemorrhage, and 1 with epiretinal membrane. Adjunctive buckle was used in 24%; 54% had 360° laser. Average number of tears seen preoperatively in those with rhegmatogenous retinal detachment was 3.1. Thirty percent had new breaks identified intraoperatively. Forty-one percent had lattice degeneration; new breaks were found in 40% of eyes with lattice. Thirteen percent of rhegmatogenous retinal detachments developed proliferative vitreoretinopathy. Average distance from the ora serrata to the vortex veins was 7.6 mm. CONCLUSION: Any eye undergoing vitrectomy may have posteriorly inserted vitreous base, but those with a high number of retinal breaks and lattice near the equator may be at highest risk. Redetachment and proliferative vitreoretinopathy still occur despite knowledge of the disorder and adjuvant treatments.
Ozulken K, Ilhan C, Yuksel E, Mumcuoglu T. Preliminary effects of treating the half of high latent hyperopia on refractive and visual results of femtosecond laser-assisted in situ keratomileusis in subjects with hyperopia. Int Ophthalmol 2020;40(9):2361-2369.Abstract
BACKGROUND: To evaluate the preliminary effects of treating the half of high latent hyperopia on refractive and visual outcomes of femtosecond laser-assisted in situ keratomileusis (LASIK) in young subjects with hyperopia. METHODS: This non-randomized comparative study includes 120 eyes of 60 subjects who underwent femtosecond LASIK to correct hyperopia. Group 1 (n = 60) includes subjects with ≤ 1D algebraic difference (DRSE) between cycloplegic (CRSE) and manifest (MRSE) refraction spherical equivalents and was treated by entering manifest refraction values. Group 2 includes subjects with > 1D DRSE and was treated by entering the mean manifest and cycloplegic refraction values. Refractive and subjective outcomes obtained at the 1-, 3-, and 6-month postoperative visits were compared. RESULTS: The mean age of the subjects was 26.2 ± 3.5 and 26.2 ± 5.2 years for Group 1 and Group 2, respectively. The male-to-female ratios were 10/10 in both groups. Demographic values of the groups were similar (p > 0.05). Preoperative MRSE values were similar (p = 0.924), while CRSE and DRSE values were significantly higher in Group 2 (p < 0.001). At the 1- and 3-month postoperative visits, MRSE was higher and uncorrected distance visual acuity (UDVA) was lower in Group 2 (p < 0.001). Subjective visual parameters and quality of vision scores were also worse in Group 2 during these visits (p < 0.001); however, at the 6-month visit, all outcomes for Group 2 improved, and MRSE, UDVA, some subjective visual parameters, and quality of vision scores became similar between groups (p > 0.05). CONCLUSION: At the 6-month visit after treating the half of > 1D latent hyperopia with femtosecond LASIK, refractive and visual outcomes like MRSE, UDVA, subjective visual parameters, and quality of vision scores become similar to those obtained in ≤ 1D latent hyperopia.

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