Histopathology of chloroquine retinal toxicity. Systemic therapy has been associated with cotton wool spots, intraretinal hemorrhages, venous occlusion, arterial occlusion, CME, and ischemic optic neuropathy. Pentosan-associated maculopathy: prevalence, screening guidelines, and spectrum of findings based on prospective multimodal analysis. Clinical and Morphologic Characteristics of MEK Inhibitor-Associated Retinopathy: Differences from Central Serous Chorioretinopathy. Bull's eye maculopathy. Rifabutin is used to treat and prevent disseminated Mycobacterium avium-complex infection. MEK inhibitors are a novel class of chemotherapeutic agents used to treat metastatic melanoma by inhibiting the MEK enzyme. ddx, retina. Regardless of the dose, patients taking thioridazine should be regularly monitored for signs of toxicity. Novak MA, Roth AS, Levine MR. Calcium oxalate retinopathy associated with methoxyflurane abuse. Cone dystrophy may present as an autosomal ⦠Their report included an additional 17 patients that presented with new features of this disease. "Unilateral Acute Idiopathic Maculopathy. The retinopathy is progressive as is high myopia. Fluorescein angiography: bilateral pig-mentepithelial transmission defects (Fig. Methods: We present a case report of a patient with a characteristic maculopathy and describe the multimodal retinal imaging findings including spectral domain optical coherence tomography and fundus autofluorescence and full-field electrophysiology. Chlorpromazine binds strongly to melanin and can also cause hyperpigmentation in the skin, conjunctiva, cornea, and lens. Checkpoint inhibitors are a targeted form of cancer immunotherapy aimed at activating the immune system against cancer cells. Mahon GJ, Anderson HR, Gardiner TA. The most commonly described ocular manifestation associated with MEK inhibitors is bilateral multifocal serous retinal detachment with at least one focus involving the fovea. Medications in this drug class include sulfa antibiotics, acetazolamide, chlorthalidone, disothiazide, ethoxyzolamide, hydrochlorothiazide, metronidazole, sulphonamide, topiramate, and triamterene. Miller FS, Bunt-Milam AH, Kalina RE. Ocular involvement in hereditary hemochromatosis is relatively rare. Cone dystrophy. The appearance can be similar to that resulting from photic damage. Drug Toxicity of the Posterior Segment. Various agents can cause cystoid macular edema including topical epinephrine, nicotinic acid, topical latanoprost, antimicrotubule agents (paclitaxel, docetaxel), fingolimod, imatinib, glitazones (rosiglitazone, pioglitazone), and trastuzumab. Drugs that damage the retinal vasculature include alkylating agents (cisplatin, BCNU), talc, oral contraceptives, intravitreal aminoglycosides, intracameral vancomycin, interferon, tacrolimus, gemcitabine, methamphetamine/cocaine, ergot alkaloids, and over-the-counter phenylpropranolamine. Methoxyflurane is an inhaled anesthetic. Chloroquine and its derivative, hydroxychloroquine sulfate, were initially used as malarial prophylaxis. Shop for Vinyl, CDs and more from BULL$EYE at the Discogs Marketplace. Most patients are typically asymptomatic with a normal FA. [32][33] Patients with low CD4 counts and higher levels of viremia on antiretroviral therapy are at increased risk for developing cidofovir-associated uveitis. Thioridazine and chlorpromazine are two agents in the phenothiazine drug class used as antipsychotics to treat schizophrenia and other psychiatric conditions. The five patients with bull's-eye maculopathy along with a negative ERG had differing genotypes. This page has been accessed 53,193 times. The American Academy of Ophthalmology released updated guidelines for screening in 2016. Various agents can cause toxicity by damaging the retinal vasculature with either direct particle clogging of blood vessels, induction of a hypercoagulable state, or both. Raza A, Mittal S, Sood GK. Partial, and sometimes complete, resolution of injury is possible after drug abuse cessation. METHODS: Clinical case report and literature review. [21][22] Patients who undergo inadvertent injection should undergo immediate pars plana vitrectomy and lavage. Visual function and macular edema typically improve after drug cessation, though the crystalline deposits remain. On FFA â window defect due to RPE atrophy Irreversible Established maculopathy - moderate reduction VA (6/18-6/24), Bullâs eye lesion in the macula Severe maculopathy - marked [eyewiki.aao.org] choroidal dystrophy (central areolar choroidal selerosis, central areolar choroidal atrophy ) AD 3rdâ5th decades Decreased central vision (20/25â20/200) Mild ⦠Symptoms include blurred vision, dyschromatopsia, nyctalopia, and visual field scotomas depending on disease severity. A preceding flu-like illness has been reported in several cases and elevated Coxsackie Virus titers were reported in a patient presenting with bilateral disease. [PubMed], Ghazi,Nicola G., MD, Armand Daccache, MD, and Brian P. Conway, MD. Acute Idiopathic Maculopathy classically presents as an abrupt, severe loss in vision (visual acuity 20/200 or worse) in one or both eyes in young, otherwise health individuals. The ⦠Loss of RPE pigmentation with accumulation of pigment-laden cells in the outer retinal layers and damage and reduction of photoreceptors. PURPOSE: To report a very rare case of bilateral Bull's eye maculopathy caused by sertraline. Francis JH, Habib LA, Abramson DH, et al. Ryan EH, Jr., Jampol LM. De La, and Rubén Cuadrado. [25] High doses (60-100 mg/day) may manifest as early as 1 year after initiation of treatment while lower doses (10-20 mg/day) may take years to manifest. The mechanism of AIM is not fully understood, although it is thought to contain an inflammatory component. New England Journal of Medicine. Corneal toxicity may include vortex keratopathy. Talk:Drug induced maculopathy. After surgery, they should be placed in an upright position to prevent gravity from directing remaining drug molecules to the posterior segment. Tamoxifen is an anti-estrogen agent used to treat certain types of cancer. Intravenous and intravitreal cidofovir have been associated with anterior uveitis, hypotony, and vision loss. We report a case of bull's eye maculopathy in a patient with hereditary hemochromatosis with no previous exposure to iron chelators and no known inherited retinal dystrophy. Explore releases from BULL$EYE at Discogs. Changes typically present 4-8 weeks after initiation of therapy and usually resolve after treatment cessation. Ocular involvement in hereditary hemochromatosis is relatively rare. Hypotony may be defined both statistically and clinically. Add to My Bookmarks. Hewas first seen in Moor-fields EyeHospital in March ⦠Hisvision was 6/9 right, 6/6 left with paracentral scotomata. Clinical use of intravitreal antibiotics to treat bacterial endophthalmitis. Bull's-eye maculopathy - American Academy of Ophthalmology Forty-seven year-old male patient with medical history of psoriatic arthritis treated with chloroquine. Epub 2018 Jun 19. Maculopathy is a pathologic condition of the macula, which is the centermost part of the retina and is responsible for highly sensitive vision. [6]While vision loss at onset is severe and abrupt in nature, spontaneous resolution and recovery of vision is expected. Human immunodeficiency virus has also been implicated. The most commonly reported side effect is an anterior uveitis, though panuveitis and Vogt-Koyanagi-Harada (VKH)-like uveitis have also been reported. Canthaxanthine is a naturally occurring carotenoid that can be used as a food-coloring agent, treatment for vitiligo/photosensitivity disorders, and tanning agent. DOI: 10.1056/NEJMicm0708021. AtLee WE. Hyporeflective exudation and subretinal fluid with detachment and disruption of photoreceptor outer segment can also be seen. Diagnosis may depend on characteristic ERG changes, including a depressed full-field photopic ERG. These findings did not alter the disease course. Peyman GA, Vastine DW, Crouch ER. If used for extended periods of time, calcium oxalate crystals can deposit in the kidneys and other tissues. Retinal toxicity or abnormality can be induced by usage of various medications. N Engl J Med 2009; 360:2224. Venkat AG, Arepalli S, Sharma S, et al. Other forms of toxicity can also include serous retinal detachments (MEK inhibitors) and retinal edema and atrophy (quinine). [2]It presents as a sudden, severe unilateral central vision loss most commonly following a flulike illness. OCT will acutely show inner retinal edema with subsequent thinning. ", International Ophthalmologists contest rules, Koushik Tripathy, MD (AIIMS), FRCS (Glasgow), https://eyewiki.org/w/index.php?title=Acute_Idiopathic_Maculopathy&oldid=68191. View; Mark Complete; Remove; Comments. No single diagnostic test can reliably detect retinopathy. They. Chloroquine causes lysosomal dysfunction in neural retina and implications for retinopathy. Other ocular changes may involve the cornea, lens, and uvea. Chloroquine retinopathy, is a form of toxic retinopathy (damage of the retina) caused by the drugs chloroquine or hydroxychloroquine, which are sometimes used in the treatment of autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus. Three months after onset, bullâs eye maculopathy appeared in the right eye (middle); however, the left eye remained normal (right). ", Fuente, Miguel A. Medications linked to maculopathy have been found to disrupt metabolic functions of the RPE and photoreceptors. The Academy uses cookies to analyze performance and provide relevant personalized content to users of our website. Kwak EL, Bang YJ, Camidge DR, et al. Witkin AJ, Chang DF, Jumper JM, et al. Treatment can include corticosteroids, drug dose adjustment, or drug discontinuation. [3][12] Also, the various macular dystrophies should be considered, however, the progressive loss of vision and pigmentary changes associated with SRF can help distinguish them from AIM. Symptoms usually resolve after discontinuation of the inciting medication. If vision loss is severe and uncontrolled, the drug can be stopped. Mutations were found in the CRX gene (2 patients), the ABCA4 gene (1 patient), and the GUCY2D gene (2 patients). Ehrenfeld M, Nesher R, Merin S. Delayed-onset chloroquine retinopathy. It may result from drug toxicity or hereditary conditions (e.g. Hypotony after intravenous cidofovir therapy for the treatment of cytomegalovirus retinitis. Chloroquine toxicity in the human eye. Correlation between cidofovir-associated uveitis and failing immunorestoration during HAART. Yasha S. Modi, M.D., and Rishi P. Singh, M.D. An ischemic retinopathy may develop with capillary nonperfusion, microaneurysm formation, cotton wool spots, venous loops, and eventual neovascularization may develop. Jump to: navigation. Ivanina TA, Zueva MV, Lebedeva MN, Bogoslovsky AI, Bunin AJ. The diagnosis of this disease is clinical and supported by ancillary testing including Optical Coherence Tomography (OCT) and Fluorescein Angiography (FA). The fluid characteristics seen on SD-OCT can be described as dome, caterpillar, wavy, and splitting. Alkyl nitrites are a group of volatile inhaled substances of abuse colloquially known as "poppers." Retinal macular dystrophy type 2 is a rare, genetic macular dystrophy disorder characterized by slowly progressive ''bull's eye'' maculopathy associated, in most cases, with mild decrease in visual acuity and central scotomata. These features can be helpful in distinguishing the MEK inhibitor associated serous detachments from central serous chorioretinopathy (CSR). Initially, the it was reported to present unilaterally and associated with a viral prodromal illness. Links to Coxsackie virus ha⦠The differential diagnosis of Acute Idiopathic Maculopathy includes diseases that present with a focal area of subretinal fluid (SRF) leading to profound central vision loss. ⦠SD-OCT is extremely helpful in detailing the extent and location of the serous detachments. Cerletti A, Taeschler M, Weidmann H. Pharmacologic studies on the structure-activity relationship of hydroxyindole alkylamines. However, permanent or progressive vision loss may occur in a few instances even despite drug cessation. [27] Histologically, they are found in the inner retina and RPE. Chloroquine and Hydroxychloroquine Are Novel Inhibitors of Human Organic Anion Transporting Polypeptide 1A2. Interferon is used in the treatment of various malignancies. [7] The most notable updates included recommendations for screening the extramacular region of Asian patients and revision of the recommended daily doses based on real body weight. Image License and Citation Guidelines. right normal; left bull's eye maculopathy. The clinical definition of hypotony is IOP low enough to result in vision loss. The Ophthalmic News and Education Network, American Academy of Ophthalmology. Courtesy of Joana Portelinha, MD File Size: 360 KB. 1991;109:1411â1416. The exact mechanism of toxicity is unknown, though it may involve enyzme disruption resulting in abnormal rhodopsin synthesis. Treatment can involve topical, local, or systemic corticosteroid therapy depending on the severity of inflammation. [30][31] The uveitis is usually bilateral, anterior, and can cause a hypopyon, simulating infectious endophthalmitis. [7]. Unilateral Acute Idiopathic Maculopathy patients present with a profound painless, central vision loss that is acute in nature. Bullâs-Eye Maculopathy Associated with Hydroxychloroquine List of authors. [12] Patients presumed to have Acute Idiopathic Maculopathy should be observed clinically and with ancillary testing for spontaneous resolution. [4]. Factors that can worsen the toxicity include an intravitreal injection with the needle bevel pointed towards the posterior pole and increased rate of injection. [10][11] Swept- Source Ocular Coherence Tomography (SS-OCT) demonstrates similar findings. In the advanced stages of toxicity, the pigment abnormalities can involve the peripheral retina with a clinical picture that resembles primary tapetoretinal degeneration with optic disc pallor, retinal vessel attenuation, and bone spicules. Wang D, Au A, Gunnemann F, et al. The papillitis occurred as both a primary disease and as an extension of the maculopathy, and the four patients presenting with eccentric macular lesions had better visual acuity than typical for AIM owing to the extrafoveal nature of their disease. Freund KB, Yannuzzi LA, Barile GR, Spaide RF, Milewski SA, Guyer DR. Symptoms that may eventually develop include paracentral scotoma, decreased visual acuity, metamorphopsia, and photophobia. [24] The exact mechanism of toxicity is unknown but thought to involve impaired retinal microcirculation. The Expanding Clinical Spectrum of Unilateral Acute Idiopathic Maculopathy. More recently, AIM was described in a 59 year old patient, 30 days after developing with yellow fever disease. , search. The superficial and deep layers of the retinal capillary plexus were preserved and a dark pattern at the choriocapillaris segmentation line was observed when compared to the right eye.[10]. Cone-rod dystrophy. SD-OCT is extremely helpful in diagnosis and can reveal subfoveal damage ranging from IS/OS junction disruption to vitelliform-like lesions to IS/OS microhole defect. Melles RB, Marmor MF. [19] The mechanism is thought to be due to RPE induced dysfunction with subsequent accumulation of subretinal fluid. Hugo Mesquita Nogueira, M.D., and Rita Dinis Gama, M.D. Indocyanine green angiography shows a hypofluorescent lesion with some hyperfluorescence in the mid-late phase. Rosenthal AR, Kolb H, Bergsma D, Huxsoll D, Hopkins JL. PATIENT: A 14-year-old girl. [10], A case report using Swept-Source Ocular Coherence Tomography Angiography demonstrated early irregular hyperfluourescence and hypofluorescence at the level of the retinal pigment epithelial lesion, followed by complete staining of the overlying neurosensory retinal detachment in the late phase of the study. Common symptoms include blurred vision, difficulty reading, metamorphopsia, paracentral scotomas, and prolonged dark adaptation. Wang L, Damji KF, Chialant D, Hodge WG. Kim HA, Lee S, Eah KS, Yoon YH. Ancillary testing may be helpful in making the diagnosis and distinguishing this entity from macular telangiectasia type 2, which can appear similar to tamoxifen retinopathy in its early stages. Overall prevalence has been calculated around 7.5%, according to one study, though this varies with duration of use and daily dose. A minority of patients treated with higher doses (300 to >450 mg/day) can develop uveitis 2 weeks to 14 months after treatment initiation. Glistening crystals located in the end arterioles is the typical appearance. Ocular Pathology/Oncology View Full Image. Intravitreal injection of aminoglycoside antibiotics is extremely toxic to the posterior segment. ", Yannuzzi LA, Jampol LM, Rabb MF, Sorenson JA, Beyrer C, Wilcox LM., Jr Unilateral acute idiopathic maculopathy. Uveitis associated with concurrent administration of rifabutin and lopinavir/ritonavir (Kaletra). Vancomycin-Associated Hemorrhagic Occlusive Retinal Vasculitis: Clinical Characteristics of 36 Eyes. Historically, AIM has been misdiagnosed and interventions such as photodynamic therapy, systemic corticosteroids and intravitreal triamcinalone have been prescribed. This page was last edited on February 21, 2021, at 20:59. Xu C, Zhu L, Chan T, et al. The Academy uses cookies to analyze performance and provide relevant personalized content to users of our website. [3][4] While his report discussed unilateral vision loss, bilateral disease has been reported as well leading some to propose renaming the disease Acute Idiopathic Maculopathy (AIM). [7], Acute Idiopathic Maculopathy classically presents as an abrupt, severe loss in vision (visual acuity 20/200 or worse) in one or both eyes in young, otherwise health individuals. The possible relationship between AIM and APMPPE has been suggested due to the overlap of many common features including the rapid onset and resolution of symptoms and the following of a prodromal flu-like illness. Usually, only the central retina is involved, however some cases of more widespread rod and cone anomalies have been reported. Authors Kamal Mtanes, Michael Mimouni, Shiri Zayit-Soudry. It has also been associated with an increased risk of immune recovery uveitis. Thioridazine toxicity at dosages less than 800 mg/day is rare, though cases have been reported with lower doses over several years. The risk of toxicity with PPS rises significantly in patients exposed to greater than 1500 g.[18] The average reported duration of therapy at time of presentation ranged from 15 to 20 years and average cumulative dose ranged from 2263 to 3375.4 g. Some experts have recommended screening to include an initial baseline exam with OCT, NIR, FAF imaging, and annual follow-up, though no consensus guidelines have been published. Local therapy for cancer therapy-associated uveitis: a case series and review of the literature. Subretinal exudation was noted in two patients and was thought to represent subretinal inflammatory cells or debris. AIM is a different entity as there is not currently an associated cause linked to its onset. "Acute Idiopathic Maculopathy. Ramsey MS, Fine BS. 2019 Aug;139(1):45-57. doi: 10.1007/s10633-019-09694-7. Bullâs-Eye Maculopathy Hugo Mesquita Nogueira, M.D. Experimental intravitreal gentamicin. Adapted from Zhu I, Andreoli MT, Mittra RA, et al. Treatment is targeted at controlling inflammation and preventing hypotony, including topical corticosteroids, cycloplegics, ibopamine, and oral probenecid. In the advanced stages of toxicity, the pigment abnormalities can involve the peripheral retina with a clinical picture that resembles primary tapetoretinal degeneration with optic disc pallor, retinal vessel attenuation, ⦠[23] Clinical examination will show intraretinal hemorrhage, vascular occlusion, and retinal ischemia. The early fundus changes often progress despite discontinuation of the drug. Zachary IG, Forster RK. Visual acuity was of counting fingers. In most cases, the CME will resolve with discontinuation of the medication. Nicolo M, Rosa R, Musetti D, Musolino M, Traverso C. Early Swept-Source Optical Coherence Tomography Angiography Findings in Unilateral Acute Idiopathic Maculopathy. The imaging changes induced by chloroquine derivatives are nonspecific and often a multimodal imaging approach is utilized with the results interpreted in the appropriate clinical context. The intraretinal hemorrhages observed in some acute lesions are thought to be secondary to venous stasis produced by optic nerve inflammation or by concomitant phlebitis. Benign concentric annular macular dystrophy. Herein we report the case of an individual who developed a bull's-eye maculopathy after ingesting uva ursi, a known inhibitor of melanin synthesis. In the posterior segment, the most common manifestation is uveitis, typically anterior with or without CME though posterior uveitis, panuveitis, retinal vasculitis, serous retinal detachments, and others have also been described. Visual acuity is affected when the pigmentary abnormalities involve the center of the fovea. Ceroid lipofuscinosis . Wetterholm DH, Winter FC. Toxicity is typically reported after chronic use of the drug (>15 years). Links to Coxsackie virus have been established, and an association with pregnancy (one case in the first trimester and one four weeks postpartum) has been observed. Cidofovir is a nucleotide analogue that inhibits viral DNA polymerase and is used in the treatment of CMV retinitis. Onset can occur days to weeks after initiation of therapy. Three months after onset, a slight pigmentary granularity appeared at the macula in the right eye, and the bullâs eye maculopathy became gradually more apparent (Fig 1B). 2018 Sep 20;55(5):312-318. doi: 10.3928/01913913-20180405-01. Bull's eye maculopathy associated with hereditary hemochromatosis We report a case of bull's eye maculopathy in a patient with hereditary hemochromatosis with no previous exposure to iron chelators and no known inherited retinal dystrophy. This may be the first case report of insidious bull's eye maculopathy exclusively identified using OCT thickness analysis, in a patient in whom both cumulative and daily dosages were under the high-risk parameters for screening and the averages reported in studies. hydroxychloroquine or chloroquine toxicity, Stargardt disease, cone dystrophy, cone-rod dystrophy, [10] Additional risk factors for toxicity include co-existing renal dysfunction and concurrent use of tamoxifen. Notably, the CME seen with nicotinic acid and the antimicrotubule agents paclitaxel and doxetaxel do not leak on FA. Related: Bull's eye maculopathy, Chloroquine retinal toxicity. Chlorpromazine retinal toxicity is rare and typically only occurs when massive doses are given (i.e., >2400 mg/day). BRAF inhibitors are small molecule inhibitors that target the BRAF protein and are used in the treatment of metastatic cutaneous melanoma. ⦠a term enclosing an heterogeneous group of phenotypes of degenerative eye diseases caused by the BEST genes No medical therapy is indicated as the maculopathy resolves on its own over the course of several days to weeks. [4] Other findings included papillitis and eccentric macular lesions. Chloroquine retinopathy in the rhesus monkey. RESULTS: A 14-year-old girl with no significant medical history developed bilateral Bull's eye maculopathy after taking sertraline for 1 year. Lin HC, Lu PL, Chang CH. Fenestrated sheen macular dystrophy. Graefes Arch Clin Exp Ophthalmol. Classically, an exudative retinal detachment of the macula is observed on exam. maculopathy, bull's eye An ocular condition in which degeneration of the retinal pigment epithelium in the macular area causes alternating ring-like light and dark zones of pigmentation, as in a target. [29] Treatment of inflammation includes topical, local, or systemic corticosteroids. Drugs can be directly toxic to the cells of the retina or the retinal pigment epithelium (RPE). Early toxicity may be asymptomatic. In the majority of instances, toxicity is reversible following discontinuation of the inciting drug. [7] In 1996, Freund, et al expanded the clinical spectrum of the maculopathy described by Yannuzzi, et al. [13][14] Thioridazine has a piperidyl side chain and is much more likely to cause toxicity than chlorpromazine. Visual acuity and color vision may be decreased. Ryan Retina. Maculopathy or macular degeneration is painless. doi: 10.1007/s00417-005-1172-3, Gupta, A., S. Rogers, and B. N. Matthews. International Ophthalmologists contest rules, Koushik Tripathy, MD (AIIMS), FRCS (Glasgow), The National Registry of Drug-Induced Ocular Side Effects, https://www.aao.org/clinical-statement/revised-recommendations-on-screening-chloroquine-h, https://eyewiki.org/w/index.php?title=Drug_induced_maculopathy&oldid=64708. [16] Women are more commonly affected due to the increased prevalence of interstitial cystitis compared to men. Fields: unchanged. Drug-induced acute transient myopia with retinal folds. Interferon-associated retinopathy during the treatment of chronic hepatitis C: a systematic review. These included a man with confluent drusen ⦠Signs include parafoveal pigmented deposits at the level of the RPE, vitelliform deposits, and patchy paracentral RPE atrophy similar in appearance to pattern dystrophy. Arch Ophthalmol. Central areolar choroidal atrophy. It notably affects younger Caucasian individuals and it appears to split equally between sexes. Patients with high BMI and dyslipidemia are at higher risk to develop tamoxifen retinopathy. Coxsackie Virus titers may be obtained as these have been elevated in patients at time of diagnosis. Dideoxyinosine (DDI)DeferoxamineRitonavir, Alkylating agentsCorticosteroid preparationsPotassium or sodium iodate, Methamphetamine and cocaineErgot alkaloidsPhenylpropanolamine.
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