Survey of Ophthalmology

Vision loss with clinical findings that are incompatible with the symptoms and recognized neurological or ophthalmic conditions is a common presentation of patients to neurologists, ophthalmologists, and neuro-ophthalmologists. The accepted terminology to describe such patients has evolved over time, including functional visual disorder (FVD), non-organic vision loss, non-physiologic vision loss, functional vision loss, psychogenic, psychosomatic, and medically unexplained visual loss. Likewise, attitudes and recommended management options have changed over the years in the fields of psychiatry and neurology. FVD is a diagnosis of inclusion, and it is critical that the diagnosis be made and delivered efficiently and effectively to reduce patient and physician duress. We review the current Diagnostic and Statistical Manual (DSM V) terminology and the prior literature on FVD and describe how the approaches to diagnosis and management have changed. We provide recommendations on the appropriate techniques and diagnostic approach for patients with FVD. We also propose a protocol for consistent and standardized discussion with the patient of the diagnosis of FVD. We believe that the adoption of FVD as both a paradigm and nomenclature shift in ophthalmology will improve patient care.

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Molecular mechanisms and treatments for ocular symblephara

AditiSwarupPhDChristopher N.TaMDAlbert Y.WuMD, PhD, FACS

doi : 10.1016/j.survophthal.2021.04.008

Volume 67, Issue 1, January–February 2022, Pages 19-30

There are currently no effective methods to prevent or durably treat ocular symblephara, the adhesions between the palpebral and bulbar conjunctiva. How symblephara form at the molecular level is largely unknown. We present here an overview of current clinical symblephara treatments and describe potential molecular mechanisms behind conjunctival adhesion formation that may inform future symblephara treatment and prevention options. Understanding how symblephara form at the molecular level will facilitate treatment development. Preventative therapies may be possible by targeting symblephara progenitor cells immediately after injuries, while novel therapeutics should be aimed at modulating TGF-? pathways and effector cells in conjunctival scarring to treat symblephara formation more effectively.

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Imaging of vascular abnormalities in ocular surface disease

VitoRomanoMDab†BernhardStegerMDc†MohammadAhmadFRCOphthaGiuliaCocoMDadLucaPaganoMDaeSajjadAhmadPhDfYitianZhaoPhDbgYalinZhengPhDbStephen BKayeMDab

doi : 10.1016/j.survophthal.2021.05.001

Volume 67, Issue 1, January–February 2022, Pages 31-51

The vascular system of the ocular surface plays a central role in infectious, autoimmune, inflammatory, traumatic and neoplastic diseases. The development, application, and monitoring of treatments for vascular abnormalities depends on the in vivo analysis of the ocular surface vasculature. Until recently, ocular surface vascular imaging was confined to biomicroscopic and color photographic assessment, both limited by poor reproducibility and the inability to image lymphatic vasculature in vivo. The evolvement and clinical implementation of innovative imaging modalities including confocal microscopy, intravenous, and optical coherence tomography–based angiography now allows standardized quantitative and functional vascular assessment with potential applicability to automated analysis algorithms and diagnostics.

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A review of filamentary keratitis

MenachemWeissMDRyanMolinaBSChibuikeOfoegbunaBSDaniel A.JohnsonMD, MBAAhmadKheirkhahMD

doi : 10.1016/j.survophthal.2021.04.002

Volume 67, Issue 1, January–February 2022, Pages 52-59

Filamentary keratitis (FK) is characterized by the presence of filaments on the corneal surface that are often associated with symptoms of foreign body sensation, irritation, and eye pain. FK is associated with a variety of ocular and systemic conditions, most notably dry eye disease. These filaments are composed primarily of epithelium, mucus, and cellular debris; however, their pathogenesis remains an area of debate. Aggravating factors for FK include desiccation, inflammatory mediators, as well as eyelid mechanical forces. Management consists of addressing associated conditions, especially dry eye disease, and providing medical and procedural treatments to alleviate symptoms and restore the ocular surface. Mainstay treatments include filament removal, increased lubrication with artificial tears and punctal occlusion, hypertonic saline, antiinflammatory and mucolytic medications, and autologous serum eye drops, as well as bandage contact lenses. A stepwise approach is required to manage patients with acute or chronic FK. Prolonged therapy is often necessary to prevent recurrence of this bothersome condition.

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Corneal collagen as a potential therapeutic target in dry eye disease

Robert O.BarattaMDaEricSchlumpfaBrian J. DelBuonoPhDaShawnDeLoreyaDavid J.CalkinsPhDb

doi : 10.1016/j.survophthal.2021.04.006

Volume 67, Issue 1, January–February 2022, Pages 60-67

Dry eye disease (DED) is a major cause of ocular discomfort, inflammation and dysfunction worldwide. Tear film instability in DED both causes and is exacerbated by disruption of the corneal epithelium. This tandem leads to a cycle of inflammation at the corneal surface involving immune cell dysregulation and increased chemokines and cytokines, which activate mitogen-activated protein kinases in the epithelium and elevates matrix metalloproteinases (MMPs). We review evidence suggesting that corneal collagen might be highly susceptible in DED to MMP-induced disruption, digestion, and thinning. We also summarize that collagen is far from inert and contains binding sites that serve as ligands for multiple inflammatory and immune regulators. Fragmented collagen not only challenges these receptor-ligand binding relationships, but also can promote recruitment and motility of pro-inflammatory immune cells. Current physician-directed therapies for DED focus on reducing inflammation, but do not directly ameliorate the underlying corneal damage that could exacerbate surface inflammation. We argue that an important gap in practice is lack of a direct therapeutic reparative for damaged corneal collagen, which is slow to heal, and likely amplifies sight-threatening inflammation. Healing fragmented collagen in the cornea may represent a more effective means to interrupt the “vicious cycle” of inflammation in DED and other conditions that damages, sometimes irreversibly, the ocular surface.

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Optical coherence tomography angiography in central serous chorioretinopathy: The current clinical role and future perspectives

AmarPujariMDAbhidnyaSurveMDShorya VardhanAzadMDAbhijeetBeniwalMBBSVikasSJMDRohanChawlaMD, FRCSAnushaSachanMDAmanKumarMDAtulKumarMD, FRCS

doi : 10.1016/j.survophthal.2021.05.003

Volume 67, Issue 1, January–February 2022, Pages 68-82

Optical coherence tomography angiography (OCTA) images the layers of retinal and choroidal vasculature in the absence of an injectable dye. Since its introduction, OCTA has been utilized in various posterior segment diseases, including central serous chorioretinopathy. We provide a comprehensive review of OCTA's application to central serous chorioretinopathy published between 2014 and 2020.

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Pentosan polysulfate maculopathy

AaronLindeke-MyersMDaAdam M.HanifMDbNierajJainMDc

doi : 10.1016/j.survophthal.2021.05.005

Volume 67, Issue 1, January–February 2022, Pages 83-96

Pentosan polysulfate sodium (PPS), a semisynthetic sulfated polysaccharide, is the only FDA-approved oral therapy for interstitial cystitis. Recent studies have described a progressive, vision-threatening macular condition associated with long-term PPS use. We reviewed all publications concerning PPS maculopathy to consolidate known clinical features and to evaluate the strength of this association. Current literature supports a strong dose-dependent association between PPS exposure and a progressive maculopathy impacting the retinal pigment epithelium (RPE) and RPE-photoreceptor interface that may worsen even after drug cessation. Initial symptoms may include prolonged dark adaptation and difficulty reading with relative visual acuity preservation. Fundus examination often shows macular pigment clumps corresponding to lesions of focal RPE thickening. Fundus autofluorescence most clearly depicts the condition, with a distinctive pattern of hypo- and hyperautofluorescent spots in the posterior pole that sometimes extends to the retinal periphery. Many cases also show a characteristic peripapillary hypoautofluorescent halo. Near infrared reflectance may aid in early detection. RPE atrophy, cystoid macular edema, and macular neovascularization may also occur, potentially resulting in loss of central acuity. This newly described association implies significant public health risk. Ophthalmologists should screen PPS users with multimodal retinal imaging, and prescribers should minimize dose and duration of PPS use.

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Retinal toxicities of systemic anticancer drugs

SupriyaAroraMS, FICO, FAICO (vitreoretina)aThamolwanSurakiatchanukulMDbTarunAroraMD, FICOacMarie HeleneErreraMDdHiteshAgrawalMSeMarcoLupidiMD, PhDf2JayChhablaniMDg1

doi : 10.1016/j.survophthal.2021.05.007

Volume 67, Issue 1, January–February 2022, Pages 97-148

Newer anticancer drugs have revolutionized cancer treatment in the last decade, but conventional chemotherapy still occupies a central position in many cancers, with combination therapy and newer methods of delivery increasing their efficacy while minimizing toxicities. We discuss the retinal toxicities of anticancer drugs with an emphasis on the mechanism of toxicity. Uveitis is seen with the use of v-raf murine sarcoma viral oncogene homolog B editing anticancer inhibitors as well as immunotherapy. Most of the cases are mild with only anterior uveitis, but severe cases of posterior uveitis, panuveitis, and Vogt-Koyanagi-Harada-like disease may also occur. In the retina, a transient neurosensory detachment is observed in almost all patients on mitogen-activated protein kinase kinase (MEK) inhibitors. Microvasculopathy is often seen with interferon ?, but vascular occlusion is a more serious toxicity caused by interferon ? and MEK inhibitors. Crystalline retinopathy with or without macular edema may occur with tamoxifen; however, even asymptomatic patients may develop cavitatory spaces seen on optical coherence tomography. A unique macular edema with angiographic silence is characteristic of taxanes. Delayed dark adaptation has been observed with fenretinide. Interestingly, this drug is finding potential application in Stargardt disease and age-related macular degeneration.

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Serous retinal detachment as a sign of leukemic choroidopathy: A systematic review

AgustinaAdaniyaMDabAndreas DiLucianoMDabRosaAlvarado-VillacortaMD, MSc(c)bcMario J.SaraviaMD, PhDdVirgilioMorales-CantónMDaPabloBazterrecheaMDeBernardo ArielSchlaenMD, PhD.e

doi : 10.1016/j.survophthal.2021.04.007

Volume 67, Issue 1, January–February 2022, Pages 149-167

Leukemia is a rare disease associated with a high mortality rate. The presence of unilateral or bilateral serous retinal detachment (SRD) as a sign of choroidal infiltration can be one of the manifestations of acute leukemia, both as a primary sign or in a relapse. We consolidated the literature on SRD as a sign of leukemic choroidopathy regarding its epidemiology, clinical manifestations, and main imaging diagnostic tools. Well-documented cases regarding acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), relapsed ALL and relapsed AML published until September, 2020, in peer reviewed journals were included. The literature shows an interesting range of choroidal infiltration cases assessed by modern imaging techniques, such as optical coherence tomography (OCT) with and without enhanced depth imaging (EDI) and fluorescein angiography (FA). These tools allow choroidal assessment and better understanding and characterization of this rare condition. Complete ophthalmological workup should be performed in these patients using both FA and EDI-OCT to assess the choroidal anatomy and integrity. An increase in choroidal thickness measured with EDI-OCT can reveal active disease and potentially diagnose a leukemic relapse promptly.

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Diabetic retinopathy, oxidative stress, and sirtuins: an in depth look in enzymatic patterns and new therapeutic horizons

MarcellaNebbiosoMDAlessandroLambiaseMD, PhDMartaArmentanoMDGiosuèTucciaroneMDMartaSacchettiMD, PhDAntonioGrecoMDLudovicoAlisiMD

doi : 10.1016/j.survophthal.2021.04.003

Volume 67, Issue 1, January–February 2022, Pages 168-183

Diabetic retinopathy (DR) is one of the leading causes of blindness in the world. DR represents the most common microvascular complication of diabetes, and its incidence is constantly rising. The complex interactions between inflammation, oxidative stress, and the production of free oxygen radicals caused by prolonged exposure to hyperglycemia determine the development of DR. Sirtuins (SIRTs) are a recently discovered class of 7 histone deacetylases involved in cellular senescence, regulation of cell cycle, metabolic pathways, and DNA repair. SIRTs participate in the progress of several pathologies such as cancer, neurodegeneration, and metabolic diseases. In DR sirtuins 1,3,5, and 6 play an important role as they regulate the activation of the inflammatory response, insulin sensibility, and both glycolysis and gluconeogenesis. A wide spectrum of direct and indirect activators of SIRTs pathways (e.g., antagomiR, resveratrol, or glycyrrhizin) is currently being developed to treat the inflammatory cascade occurring in DR. We focus on the main metabolic and inflammatory pathways involving SIRTs and DR, as well as recent evidence on SIRTs activators that may be employed as novel therapeutic approaches to DR.

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Pars plana vitrectomy, scleral buckle, and pneumatic retinopexy for the management of rhegmatogenous retinal detachment: a meta-analysis

Marko M.PopovicMD, MPH(C)aRajeev H.MuniMD, MSc, FRCSCabPremNichaniMSc, MDcPeter J.KertesMD, FRCSCad

doi : 10.1016/j.survophthal.2021.05.008

Volume 67, Issue 1, January–February 2022, Pages 184-196

We reviewed the literature on the efficacy and safety of pars plana vitrectomy (PPV), scleral buckle (SB), and pneumatic retinopexy (PR) for the management of rhegmatogenous retinal detachments (RRDs). A systematic search was performed on three databases from inception to September 2020. Randomized controlled trials (RCTs) comparing RRD management options were included. Meta-analysis was performed using a random effects model. Eighteen RCTs and 2,751 eyes were included. For PPV versus SB, early postoperative corrected distance visual acuity (CDVA) favored SB (weighted mean <1 month postoperatively: ~counting fingers for PPV versus ~20/260 for SB, P = 0.02), but differences were nonsignificant at other time points. There was no difference for primary reattachment (P = 0.08). PPV had a lower incidence of choroidal detachment (P = 0.004), hypotony (P = 0.01), and strabismus/diplopia (P = 0.04) but a higher incidence of iatrogenic breaks (P = 0.003) and cataract development/progression (P = 0.05) relative to SB. Combination management was nonsignificantly different relative to PPV alone for CDVA, complications and reattachment rate.

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Elucidation of the role of the lamina cribrosa in glaucoma using optical coherence tomography

Julia Corradi F.AndradeMDaFábio N.KanadaniMD, PhDadRafael L.FurlanettoMD, PhDbFlavio S.LopesMDbRobertRitchMD, FACScTiago S.PrataMD, PhDbd

doi : 10.1016/j.survophthal.2021.01.015

Volume 67, Issue 1, January–February 2022, Pages 197-216

Glaucoma is a chronic and progressive optic neuropathy characterized by the death of retinal ganglion cells and corresponding visual field loss. Despite the growing number of studies on the subject, the pathogenesis of the disease remains unclear. Notwithstanding, several studies have shown that the lamina cribrosa (LC) is considered an anatomic site of glaucomatous optic nerve injury, thus having a key role in the pathophysiology of glaucoma development and progression. Different morphological alterations of the LC have been described in vivo in glaucomatous eyes after the evolution of optical coherence tomography (OCT) devices. The most relevant findings were the reduction of laminar thickness, the presence of localized defects, and the posterior LC displacement. These new laminar parameters documented through OCT are not only promising as possible additional tools for glaucoma diagnosis and monitoring, but also as predictors of disease progression. In spite of the advance of technology, however, proper evaluation of the LC is not yet viable in all eyes. We describe OCT-identified LC changes related to the development and progression of glaucoma and provide future directions based on a critical data analysis, focusing on its clinical relevance and applicability.

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Impact of COVID-19 pandemic on ophthalmology medical student teaching: educational innovations, challenges, and future directions

TonySuccarPhD, MScMed(OphthSc)abHilary A.BeaverMDcefghijkAndrew G.LeeMDcdefghijk

doi : 10.1016/j.survophthal.2021.03.011

Volume 67, Issue 1, January–February 2022, Pages 217-225

Graduate medical education (GME) in ophthalmology has faced and overcome many challenges over the past years, and 2020 has been a game-changer. Although the severe acute respiratory syndrome coronavirus pandemic disrupted medical education globally, ophthalmic educators rapidly transformed their curricula to novel and effective virtual learning formats. Thus, while the COVID-19 outbreak has been one of the most significant challenges faced in the history of medical education, it has also provided an impetus to develop innovative teaching practices, bringing with it unprecedented success in allowing medical students to continue their education in ophthalmology despite these challenges. We review and appraise novel educational interventions implemented by various institutions in response to the COVID-19 pandemic, highlighting their effectiveness, challenges and proposing future directions beyond the pandemic. Many of these innovations will persist even after the end of the pandemic because they have proven that face-to-face learning is not required for all aspects of the ophthalmic GME curriculum. As ophthalmic educators harness the power of educational technology it is critical that their novel educational initiatives are incorporated into competency-based curricula with assessments mapped to the competencies. Future research should focus on evaluating the impact of this transformation to virtual learning environments on student performances as well as implementing longitudinal assessment strategies for clinical competence in workplace-based practice.

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Animal and cadaver human eyes for residents’ surgical training in ophthalmology

AmarPujariMD#GunjanSalujaMD#KarthikaBhaskaranMDSujeethModaboyinaMDMohamed IbrahimeAsifMDTusharAgarwalMDNamrataSharmaMDJeewan S.TitiyalMD

doi : 10.1016/j.survophthal.2021.05.004

Volume 67, Issue 1, January–February 2022, Pages 226-251

In ophthalmology residency programs surgical training plays a vital role in creating confident and skillful surgeons. As almost all ophthalmic surgery needs microscope training, creating a well-taught environment for hand-eye coordination, ocular tissue handling, and anticipation of complications is essential. Wet lab training with animal or cadaver human eyes offers diverse possibilities. We conducted a thorough literature search on various databases to identify the existing literature on wet labs. The results revealed constructive efforts for training novice surgeons in all surgical ophthalmology subspecialties. Wet lab models were initially used only to practice cataract surgery; however, now various complex ocular procedures can be practiced. Ocular surface, corneal, iris, lenticular, scleral, vitreoretinal, extraocular, eyelid, and other adnexal surgeries were reproduced and mastered in many ways. Importantly, with repeated surgical practice, residents gained an increasing level of confidence with enhanced surgical accuracy. In addition, we propose a few novel techniques of various other procedures.

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Artificial intelligence: the unstoppable revolution in ophthalmology

DavidBenetMscaOscar J.Pellicer-ValeroMscb

doi : 10.1016/j.survophthal.2021.03.003

Volume 67, Issue 1, January–February 2022, Pages 252-270

Artificial intelligence (AI) is an unstoppable force that is starting to permeate all aspects of our society as part of the revolution being brought into our lives (and into medicine) by the digital era, and accelerated by the current COVID-19 pandemic. As the population ages and developing countries move forward, AI-based systems may be a key asset in streamlining the screening, staging, and treatment planning of sight-threatening eye conditions, offloading the most tedious tasks from the experts, allowing for a greater population coverage, and bringing the best possible care to every patient.

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Dural venous sinus stenting in the treatment of idiopathic intracranial hypertension: A systematic review and critique of literature

AnnaKabanovskiaEliKisilevskyMDbYelinYangMDbEdwardMargolinMDbc

doi : 10.1016/j.survophthal.2021.05.002

Volume 67, Issue 1, January–February 2022, Pages 271-287

Idiopathic intracranial hypertension (IIH) is increased intracranial pressure without a known cause. Dural venous sinus stenting (DVSS) is a relatively new intervention for treatment of IIH refractory to medical therapy and lifestyle modifications. In this review, we outline various hypotheses of IIH pathogenesis and describe the role of venous sinus stenosis and the technical details of DVSS. We also present a summary and critique of the available evidence describing the outcomes of DVSS in IIH and review the evidence-based guidelines for this procedure. We conclude that, although many studies have shown generally favorable outcomes of DVSS in patients with IIH, most have serious limitations, the most common one being paucity of pre- and postprocedure ophthalmological data. Thus, there is not enough available evidence to conclude whether DVSS is an effective procedure for treatment of IIH. We also present the most commonly used indications for DVSS as described in the literature and stress the importance of neuro-ophthalmological assessment before and after the procedure to monitor response and potential complications.

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As the worm turns: An infant with exotropia

LaurenHenneinMDaAlejandra G.de Alba CampomanesMD, MPHaArmin R.AfsharMD, MBA, MASaShira L.RobbinsMDb

doi : 10.1016/j.survophthal.2020.12.003

Volume 67, Issue 1, January–February 2022, Pages 288-292

A two-year-old full-term boy with a history of an intermittent exotropia presented to the pediatric ophthalmology clinic for routine follow-up. He was found to have a stable sensorimotor examination however dilated funduscopic examination of the right eye was significant for a dim foveal reflex with a new discrete, white, elevated retinal lesion superotemporal to the fovea with surrounding subretinal exudates. An examination under anesthesia (EUA) was performed two days later that revealed a subretinal posterior pole granuloma with hyperfluorescence and late leakage from the lesion without telangiectatic vessels on fluorescein angiography. A repeat EUA one month later demonstrated an increase in surrounding subretinal and overlying intraretinal fluid. The patient was started on topical 1% prednisolone with a presumed diagnosis of Toxocara granuloma. At EUA, three months later, the subretinal and intraretinal fluid had resolved. The topical steroids were tapered, and the patient continues to be followed closely.

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