|
1
|
Li BY, Tan W, Zou JL, He Y, Yoshida S, Jiang B, Zhou YD. Role of interferons in diabetic retinopathy. World J Diabetes 2021; 12:939-953. [PMID: 34326947 PMCID: PMC8311473 DOI: 10.4239/wjd.v12.i7.939] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 04/15/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetic retinopathy (DR) is one of the major causes of visual impairment and irreversible blindness in developed regions. Aside from abnormal angiogenesis, inflammation is the most specific and might be the initiating factor of DR. As a key participant in inflammation, interferon-gamma (IFN-γ) can be detected in different parts of the eye and is responsible for the breakdown of the blood-retina barrier and activation of inflammatory cells and other cytokines, which accelerate neovascularization and neuroglial degeneration. In addition, IFN-γ is involved in other vascular complications of diabetes mellitus and angiogenesis-dependent diseases, such as diabetic nephropathy, cerebral microbleeds, and age-related macular degeneration. Traditional treatments, such as anti-vascular endothelial growth factor agents, vitrectomy, and laser photocoagulation therapy, are more effective for angiogenesis and not tolerable for every patient. Many ongoing clinical trials are exploring effective drugs that target inflammation. For instance, IFN-α acts against viruses and angiogenesis and is commonly used to treat malignant tumors. Moreover, IFN-α has been shown to contribute to alleviating the progression of DR and other ocular diseases. In this review, we emphasize the roles that IFNs play in the pathogenesis of DR and discuss potential clinical applications of IFNs in DR, such as diagnosis, prognosis, and therapeutic treatment.
Collapse
Affiliation(s)
- Bing-Yan Li
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
- Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Wei Tan
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
- Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Jing-Ling Zou
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
- Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Yan He
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
- Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Shigeo Yoshida
- Department of Ophthalmology, Kurume University School of Medicine, Kurume 830-0011, Fukuoka, Japan
| | - Bing Jiang
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
- Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Ye-Di Zhou
- Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
- Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| |
Collapse
|
|
2
|
Retinal toxicities of systemic anticancer drugs. Surv Ophthalmol 2021; 67:97-148. [PMID: 34048859 DOI: 10.1016/j.survophthal.2021.05.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 05/08/2021] [Accepted: 05/10/2021] [Indexed: 01/07/2023]
Abstract
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 α, but vascular occlusion is a more serious toxicity caused by interferon α 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.
Collapse
|
|
3
|
M Castillejo Becerra C, Ding Y, Kenol B, Hendershot A, Meara AS. Ocular side effects of antirheumatic medications: a qualitative review. BMJ Open Ophthalmol 2020; 5:e000331. [PMID: 32154367 PMCID: PMC7045116 DOI: 10.1136/bmjophth-2019-000331] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 09/29/2019] [Accepted: 11/09/2019] [Indexed: 12/29/2022] Open
Abstract
Topic This paper reviews the ocular side effects of medications used in the treatment of rheumatological conditions. Clinical relevance Rheumatic diseases are inflammatory conditions that may affect the skin, blood vessels, joints, muscles and internal organs. Immunosuppressive agents are often used as treatment and while powerful, they carry side effects and toxicities that need careful monitoring. Ophthalmic complications have been reported with the use of antirheumatic medications; however, there is a lack of literature synthesising these reports. This paper addresses this gap and hopes to inform both rheumatologists and ophthalmologists as they work together on the management of patients with rheumatological conditions. Methods PubMed literature search was conducted from November to September 2019 searching for ocular side effects with the use of 25 rheumatological drugs. Results A total of 111 papers were included in this review. Adverse side effects were divided into non-infectious and infectious causes. Traditional disease-modifying antirheumatic drugs (DMARDs) were associated with pruritus, irritation and dryness of the conjunctiva while biologic DMARDS showed reports of new-onset/recurrent uveitis and demyelinating conditions. Infectious side effects included episodes of cytomegalovirus retinitis, toxoplasmic chorioretinitis and endophthalmitis. Other serious side effects were encountered and included in this review. Conclusion The goal of this paper is to inform healthcare providers about potential ocular side effects from rheumatological medications. Healthcare providers are encouraged to learn more about these ophthalmic complications and find relevance within their clinical practice.
Collapse
Affiliation(s)
| | - Yue Ding
- Division of Rheumatology and Immunology, Ohio State University, Columbus, Ohio, USA
| | - Beatrice Kenol
- Division of Rheumatology and Immunology, Ohio State University, Columbus, Ohio, USA
| | - Andrew Hendershot
- Department of Ophthalmology, Ohio State University, Columbus, Ohio, USA
| | - Alexa Simon Meara
- Division of Rheumatology and Immunology, Ohio State University, Columbus, Ohio, USA
| |
Collapse
|
|
4
|
Lai CH, Yang YH, Chen PC, King YC, Liu CY. Retinal vascular complications associated with interferon-ribavirin therapy for chronic hepatitis C: A population-based study. Pharmacoepidemiol Drug Saf 2017; 27:191-198. [PMID: 29210149 DOI: 10.1002/pds.4363] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Revised: 10/03/2017] [Accepted: 11/02/2017] [Indexed: 01/25/2023]
Abstract
PURPOSE To investigate the incidence of retinal vascular complications and risk factors in patients with chronic hepatitis C receiving interferon-ribavirin therapy in Taiwan. METHODS By using the Taiwan National Health Insurance Research Database, we compared the incidence of retinal vascular complications between patients receiving and not receiving interferon-ribavirin treatment. The exposure and nonexposure groups were randomly 1:1 frequency-matched according to age, sex, income, urbanization level, hypertension, and diabetes. Incidence of each retinal vascular complication and hazard ratios were assessed in the follow-up evaluation. RESULTS Of the sample of 4736 patients, a total of 182 patients (3.84%) developed retinopathy during the follow-up period, of which 110 patients (4.65%) received interferon-ribavirin therapy and 72 patients (3.04%) did not receive interferon-ribavirin therapy. After multivariate adjustments, the risk of retinopathy during the follow-up period was 1.533 (95% confidence interval [CI], 1.139-2.064; P = .0048) times higher in patients receiving interferon-ribavirin therapy than in those in the comparison cohort not receiving the therapy. Patients with hypertension compared with those without it (adjusted hazard ratio, 1.530; 95% CI, 1.069-2.135; P = .0125) also had an increased risk of retinopathy. CONCLUSIONS Interferon-ribavirin therapy was associated with a 53.3% increased risk of retinal vascular complications compared with not receiving the therapy. Regular ophthalmologic examination is essential for patients receiving interferon-ribavirin, particularly those with hypertension.
Collapse
Affiliation(s)
- Chien-Hsiung Lai
- Department of Ophthalmology, Chang Gung Memorial Hospital, Chiayi, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan.,School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yao-Hsu Yang
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.,Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi, Taiwan.,Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan
| | - Pau-Chung Chen
- Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan.,Department of Environmental and Occupational Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ying-Chi King
- Department of Ophthalmology, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chia-Yen Liu
- Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi, Taiwan
| |
Collapse
|
|
5
|
Retinal toxicities of cancer therapy drugs: biologics, small molecule inhibitors, and chemotherapies. Retina 2014; 34:1261-80. [PMID: 24949716 DOI: 10.1097/iae.0000000000000242] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE To review reported retinal side effects from current cancer therapy drugs. METHODS Retinal toxicities from ophthalmologic or oncologic case reports, case series, and clinical trials were identified by a systematic literature search using Lexicomp and PubMed. RESULTS Four biologics, 8 small molecule inhibitors, and 17 traditional chemotherapy agents had reported retinal side effects. For biologics, interferon alpha 2b was associated with retinopathy, denileukin diftitiox with pigmentary retinopathy, ipilimumab with a Vogt-Koyanagi-Harada-like syndrome, and trastuzumab with retinal ischemia. For small molecule inhibitors, v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors were associated with uveitis, mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitors with pigment epithelium detachments, and tyrosine kinase inhibitors with macular edema. Steroid antagonists were associated with crystalline retinopathy and macular edema. Nitrosoureas, platinum analogs, and cytosine arabinoside were associated with retinal vascular occlusions. Antimicrotubular agents were associated with cystoid macular edema but without fluorescein leakage. Retinoic acid derivatives were associated with impaired night vision, and mitotane was associated with a pigmentary retinopathy and papilledema. CONCLUSION Certain agents used in the treatment of systemic cancer are associated with ocular complications. Awareness of these complications will allow early detections and maybe reversal of some of the ocular problems.
Collapse
|
|
6
|
Xue JH, Zhu HH, Wang J, Chen Z. Interferon-associated retinopathy risk in patients with diabetes and hypertensive hepatitis C. World J Gastroenterol 2014; 20:7505-7513. [PMID: 24966622 PMCID: PMC4064097 DOI: 10.3748/wjg.v20.i23.7505] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Revised: 02/11/2014] [Accepted: 03/05/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the association of hypertension and diabetes mellitus (DM) with interferon-associated retinopathy (IAR) risk in chronic hepatitis C (CHC).
METHODS: Two investigators independently searched PubMed and Embase for eligible articles published prior to December 2013; additional studies were identified by reviewing the bibliographies. Only case-control or cohort studies that evaluated the association between hypertension and/or DM and IAR incidence in CHC patients were included. IAR was characterized by the presence of cotton-wool spots and/or retinal hemorrhage, and was defined as the primary efficacy measure. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were estimated using data extracted from papers based on random-effects models.
RESULTS: Eight eligible studies were included in the present meta-analysis. The outcomes showed that patients with CHC and hypertension were at higher risk of IAR (48/189 vs 96/455, RR = 1.90; 95%CI: 1.15-3.15, P < 0.05). Patients with DM receiving interferon (IFN)-based therapy for CHC infection may be at higher risk for IAR (18/72 vs 60/256, RR = 1.56, 95%CI: 1.11-2.20, P < 0.05); however, the outcome was not stable. There was no significant difference in IAR risk between genotype-1-infected patients and non-genotype-1-infected patients (RR = 1.09, 95%CI: 0.64-1.87, P > 0.05). Comparable incidences of IAR were also found between patients treated with pegylated interferon (PIFN) α-2a and those treated with PIFN α-2b (RR = 0.84, 95%CI: 0.56-1.24, P > 0.05) and between patients treated with IFN α and those treated with PIFN α (RR = 1.04, 95%CI: 0.72-1.50, P > 0.05).
CONCLUSION: Patients with hypertension have a higher risk of retinopathy when receiving IFN-based therapy for CHC.
Collapse
|
|
7
|
Al Mannai F, Qaddoura R, Derbala M. Ischemic Optic Neuropathy in Chronic Viral Hepatitis C Treated with Interferon and Ribavirin. Qatar Med J 2012. [DOI: 10.5339/qmj.2012.1.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Ischemic Optic Neuropathy (ION) is a rare complication of interferon (IFN) during treatment of Hepatitis C virus (HCV) with all reported cases occurring within three months of the start of therapy. We report a case of a late bilateral sequential ischemic optic neuropathy after 36 weeks of pegylated-interferon therapy. In contrast to previous reports, we recommend a regular ophthalmological follow-up throughout the whole course of interferon therapy.
Collapse
Affiliation(s)
- F.A. Al Mannai
- Ophthalmology Section, Department of Surgery, Hamad Medical Corporation, Doha, Qatar
| | - R.H. Qaddoura
- Ophthalmology Section, Department of Surgery, Hamad Medical Corporation, Doha, Qatar
| | - M.F. Derbala
- Ophthalmology Section, Department of Surgery, Hamad Medical Corporation, Doha, Qatar
| |
Collapse
|
|
8
|
Kang HY, Shin MC. Pegylated interferon-associated severe retinopathy in a patient with chronic hepatitis. KOREAN JOURNAL OF OPHTHALMOLOGY 2012; 26:147-50. [PMID: 22511844 PMCID: PMC3325622 DOI: 10.3341/kjo.2012.26.2.147] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2008] [Accepted: 08/04/2010] [Indexed: 11/23/2022] Open
Abstract
This paper reports a case of pegylated interferon-associated retinopathy in a patient with chronic hepatitis C. A 32-year-old female with chronic hepatitis C undergoing pegylated interferon and ribavirin combination therapy complained of visual blurring. Features of interferon-associated retinopathy, including ocular complications such as cotton wool spots, retinal hemorrhages, macular edema, and branch retinal vein occlusion, were found in the fundus of both of her eyes. Pegylated interferon combination therapy was stopped, and the retinopathy of the patient was treated with intravitreal bevacizumab injections and panretinal photocoagulations. This case shows that pharmacokinetically improved pegylated interferon has ocular complications for patients with chronic hepatitis C. Accordingly, patients undergoing pegylated interferon treatment for hepatitis C need regular eye examinations for protection of their vision.
Collapse
|
|
9
|
Kwon YD, Lim JW. Clinical Features of Retinopathy in Chronic Hepatitis B Patients With Treated With Peginterferon. JOURNAL OF THE KOREAN OPHTHALMOLOGICAL SOCIETY 2011. [DOI: 10.3341/jkos.2011.52.1.41] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Yong Dae Kwon
- Hallym University Chuncheon Sacred Heart Hospital, Chuncheon, Korea
| | - Ji Won Lim
- Hallym University Chuncheon Sacred Heart Hospital, Chuncheon, Korea
| |
Collapse
|
|
10
|
Retinopathy associated with pegylated interferon and ribavirin treatment for chronic hepatitis C. ACTA ACUST UNITED AC 2010; 81:580-6. [DOI: 10.1016/j.optm.2010.04.094] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2010] [Revised: 04/12/2010] [Accepted: 04/16/2010] [Indexed: 02/08/2023]
|
|
11
|
Kang HM, Park MJ, Hwang JM, Kim JW, Jeong SH. Development of ocular myasthenia during pegylated interferon and ribavirin treatment for chronic hepatitis C. THE KOREAN JOURNAL OF HEPATOLOGY 2009; 15:209-15. [PMID: 19581773 DOI: 10.3350/kjhep.2009.15.2.209] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.
Collapse
Affiliation(s)
- Hyung Min Kang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | | | | | | | | |
Collapse
|
|
12
|
Abstract
A 34-year-old woman developed bilateral optic neuritis 2 weeks after the onset of acute hepatitis C. The strong temporal relationship between the initial clinical manifestations of hepatitis C and the development of optic neuritis provides a basis for thinking that the hepatitis caused the optic neuritis After corticosteroid treatment, the optic neuropathy markedly improved but left behind retinal nerve fiber thinning, as measured by optical coherence tomography, and optic disc pallor. Optic neuritis has been reported in conjunction with hepatitis A and B but not with hepatitis C.
Collapse
|
|
13
|
Kang HY, Lim JW, Shin MC. Pegylated Interferon Associated Retinopathy in Chronic Hepatitis Patients. JOURNAL OF THE KOREAN OPHTHALMOLOGICAL SOCIETY 2009. [DOI: 10.3341/jkos.2009.50.3.383] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Affiliation(s)
- Hee Young Kang
- Department of Ophthalmology, Chuncheon Sacred Heart Hospital, Hallym University, School of Medicine, Gangwon, Korea
| | - Ji Won Lim
- Department of Ophthalmology, Chuncheon Sacred Heart Hospital, Hallym University, School of Medicine, Gangwon, Korea
| | - Min Chul Shin
- Department of Ophthalmology, Chuncheon Sacred Heart Hospital, Hallym University, School of Medicine, Gangwon, Korea
| |
Collapse
|
|
14
|
Interferon-alpha-associated presumed ocular sarcoidosis. Graefes Arch Clin Exp Ophthalmol 2008; 247:675-80. [PMID: 19034483 DOI: 10.1007/s00417-008-1002-5] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2008] [Revised: 11/01/2008] [Accepted: 11/05/2008] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Interferon alpha, used in the treatment of different viral, autoimmune and malignant diseases, is known to induce a variety of side effects. Recently, induction of sarcoidosis during interferon therapy has been reported. We analyzed patients for uveitis, possibly induced by interferon alpha. METHODS We report on three patients who had developed typical signs of ocular sarcoidosis under treatment with interferon alpha for chronic hepatitis C virus infection. In two patients, conventional interferon alpha was used and in another one, pegylated interferon alpha-2b. All patients additionally received ribavirin. RESULTS In all three cases, panuveitis was diagnosed. The mean duration of interferon treatment before development of uveitis was 10 months. Clinically, all patients demonstrated granulomatous panuveitis with choroidal granulomas of various sizes. In one case, the uveitis developed together with renal failure, fever and malaise. In this patient, an elevated ACE level was detected. In another patient, the diagnosis of sarcoid induced uveitis was confirmed by positive chest CT scan. The intraocular inflammation was managed with a reduction of the interferon dosage. The therapy with ribavirin was not changed. All patients received topical steroids. Systemic steroids were applied only in the case with systemic disease manifestations. CONCLUSIONS Uveitis can be a sign of sarcoidosis induced by interferon alpha. Further studies are required to support the observation that with early diagnosis the prognosis of uveitis seems to be good.
Collapse
|
|
15
|
Plskova J, Greiner K, Forrester JV. Interferon-alpha as an effective treatment for noninfectious posterior uveitis and panuveitis. Am J Ophthalmol 2007; 144:55-61. [PMID: 17601428 DOI: 10.1016/j.ajo.2007.03.050] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2006] [Revised: 03/24/2007] [Accepted: 03/30/2007] [Indexed: 12/30/2022]
Abstract
PURPOSE Several studies have shown the capacity of interferon-alpha (IFN-alpha) to control ocular Behçet disease. The authors aimed to determine whether IFN-alpha was effective in treating patients with severe, refractory sight-threatening intraocular inflammation (uveitis) from a wider range of causes, including Behçet disease. DESIGN Prospective, interventional case series. METHODS Twelve patients with sight-threatening uveitis that failed to respond to one or more immunosuppressive regimens were enrolled to this study. Recombinant human IFN-alpha-2b was administered subcutaneously daily, and the dose was adjusted according to the clinical response. Main outcome measures were visual acuity, clinical activity of uveitis (including binocular indirect ophthalmoscopy [BIO] score and presence or absence of macular edema), and adverse effects of the treatment. RESULTS The mean observation period was 11 months (range, one to 29 months). A positive clinical response was observed in 83% of patients. Median visual acuity improved from 0.54 to 0.2 (logarithm of the minimum angle of resolution units; P < .001) and median BIO score decreased from 1.0 to 0.5 (P < .05) within one month of treatment. Macular edema, if present, resolved in all patients within days of treatment. The main adverse events were tiredness, lymphopenia, flu-like symptoms, and transient increase of liver enzymes. Weight loss occurred in four patients. Four patients experienced depression, one of them attempting suicide. Three patients experienced typical features of IFN-alpha-associated retinopathy, which resolved on reducing the dose. CONCLUSIONS IFN-alpha seems to have significant potential in treatment of severe, sight-threatening refractory uveitis from a variety of causes. A range of adverse events, including IFN-alpha-associated retinopathy, may occur and could limit the use of this immunomodulatory drug.
Collapse
Affiliation(s)
- Jarka Plskova
- Department of Ophthalmology, University of Aberdeen, Aberdeen, Scotland, United Kingdom
| | | | | |
Collapse
|
|
16
|
Pérez-Alvarez MJ, Montes-Ramírez ML, Machín-Lázaro JM, Rodríguez-Zapata M. Retinopatía asociada a interferón pegilado. Enferm Infecc Microbiol Clin 2007; 25:217. [PMID: 17335705 DOI: 10.1016/s0213-005x(07)74265-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
|
|
17
|
Buster EHCJ, Ter Borg MJ, Vingerling JR, Janssen HLA. Low incidence of retinopathy during peginterferon alpha-2b and lamivudine therapy for chronic hepatitis B. J Hepatol 2006; 45:160-1; author reply 161-2. [PMID: 16723166 DOI: 10.1016/j.jhep.2006.04.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
|
|
18
|
d'Alteroche L, Majzoub S, Lecuyer AI, Delplace MP, Bacq Y. Ophthalmologic side effects during alpha-interferon therapy for viral hepatitis. J Hepatol 2006; 44:56-61. [PMID: 16223542 DOI: 10.1016/j.jhep.2005.07.026] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2005] [Revised: 07/13/2005] [Accepted: 07/15/2005] [Indexed: 12/15/2022]
Abstract
BACKGROUND/AIMS Ophthalmologic side effects have been reported during interferon therapy, particularly retinal lesions and neurovisual impairment. The aim of this prospective study was to assess the nature and the frequency of such lesions during alpha-interferon therapy for viral hepatitis. METHODS Between 1995 and 2003, 156 patients treated with standard or pegylated alpha-interferon, with or without ribavirin, had a regular ophthalmologic examination before and during treatment. No patient had signs of retinopathy before treatment. Cotton-wool spots were found in 31 patients and retinal hemorrhage in nine patients during treatment (24% of patients). These lesions remained asymptomatic and disappeared in all patients. A previous history of arterial hypertension (RR 4.60, 95% CI 1.95-10.85), age above 45 years (RR 2.80, 95% CI 1.36-5.85), and use of pegylated alpha-interferon (RR 2.75, 95% CI 1.41-5.38) were significantly associated with retinopathy. Neurovisual impairment was present in 31 patients (20%) before treatment and in 74 patients (47%) during treatment. CONCLUSIONS In conclusion, this study showed that signs of retinopathy and neurovisual impairment were common in patients receiving alpha-interferon therapy but were rarely symptomatic. It suggests that alpha-interferon may usually be continued in asymptomatic patients as long as there is careful fundoscopic examination.
Collapse
Affiliation(s)
- Louis d'Alteroche
- Service d'Hépato-Gastroentérologie, Hôpital Trousseau, 37044 Tours cedex, France.
| | | | | | | | | |
Collapse
|
|
19
|
Dimberg LY, Dimberg AI, Ivarsson K, Strömberg T, Osterborg A, Nilsson K, Oberg F, Jernberg Wiklund H. Ectopic and IFN-induced expression of Fas overcomes resistance to Fas-mediated apoptosis in multiple myeloma cells. Blood 2005; 106:1346-54. [PMID: 15860671 DOI: 10.1182/blood-2004-04-1322] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Multiple myeloma (MM) is an as-yet incurable B-cell malignancy. Increased survival in vitro is a hallmark of MM cells, implying that a therapeutic potential may lie in circumventing antiapoptotic signals. We have previously reported that interferons (IFNs) sensitize MM cells to Fas/CD95-mediated apoptosis. In the present study, we explore the mechanism underlying this effect. In a wide screening of apoptosis-related genes, Apo2L/TRAIL (tumor necrosis factor [TNF]-related apoptosis inducing ligand) and Fas were identified as IFN targets. Sensitization to Fas-mediated apoptosis by IFNs was not affected by blocking Apo2L/TRAIL, suggesting that Apo2L/TRAIL is not a key mediator in this process. In contrast, we found that an elevated Fas expression was functionally linked to increased susceptibility to Fas-mediated apoptosis. This was further supported by the finding that IFN treatment enhanced Fas-mediated caspase-8 activation, one of the earliest signaling events downstream receptor activation. In addition, IFN treatment attenuated the interleukin 6 (IL-6)-dependent activation of signal transducer and activator of transcription 3 (Stat3), interfering with a known survival pathway in MM that has previously been linked with resistance to Fas-mediated apoptosis. Taken together, our results show that IFN-induced up-regulation of Fas sensitizes MM cells to Fas-mediated apoptosis and suggest that attenuation of Stat3 activation may be a potentially important event in this process.
Collapse
Affiliation(s)
- Lina Y Dimberg
- Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
| | | | | | | | | | | | | | | |
Collapse
|
|
20
|
Chisholm JA, Williams G, Spence E, Parks S, Keating D, Gavin M, Mills PR. Retinal toxicity during pegylated alpha-interferon therapy for chronic hepatitis C: a multifocal electroretinogram investigation. Aliment Pharmacol Ther 2005; 21:723-32. [PMID: 15771758 DOI: 10.1111/j.1365-2036.2005.02365.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Ocular side-effects in the form of retinal ischaemia and haemorrhages have been reported in patients undergoing standard alpha-interferon therapy. AIM To assess the ocular impact of therapy with sustained release pegylated alpha-2a interferon (Pegasys) for chronic hepatitis C. METHODS Ten patients receiving Pegasys and ribavirin and 10 healthy volunteers were recruited. Patients underwent full ophthalmic investigations and multifocal electroretinogram testing at baseline, at regular intervals during treatment and post-treatment. The multifocal electroretinogram maps retinal function. Responses were compared with sequential recordings from healthy volunteers. RESULTS All patients had normal clinical ophthalmic investigations at baseline. During therapy a single patient experienced central visual disturbance lasting 24 h with no prolonged ill effect. No other patient was aware of any change in vision. Fundal abnormalities appeared in five patients during treatment. The multifocal electroretinogram showed reductions in retinal function in five patients. Nine of 10 patients exhibited abnormalities on at least one multifocal electroretinogram or fundoscopic investigation. CONCLUSIONS Subclinical retinal toxicity during anti-viral therapy with pegylated alpha-interferon and ribavirin was frequent in this study and it suggests that patients should be warned of this risk and monitored during therapy.
Collapse
Affiliation(s)
- J A Chisholm
- Department of Clinical Physics and Bioengineering, Gartnavel General Hospital, Glasgow G12 0YN, UK.
| | | | | | | | | | | | | |
Collapse
|
|
21
|
Cuthbertson FM, Davies M, McKibbin M. Is screening for interferon retinopathy in hepatitis C justified? Br J Ophthalmol 2004; 88:1518-20. [PMID: 15548803 PMCID: PMC1772411 DOI: 10.1136/bjo.2004.043968] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND/AIM In the treatment of hepatitis C, the National Institute for Clinical Excellence advocates use of a combination of interferon alfa and ribavirin for selected patients. Retinopathy is a well recognised side effect of interferon therapy and is characterised by retinal haemorrhages, cotton wool spots, and macular oedema. The aim of this study was to document the incidence and natural history of the retinopathy in patients treated with a long acting (pegylated) interferon and ribavirin for hepatitis C and to assess the need to screen for retinal complications. METHODS All patients started on treatment from September 2002 to August 2003 were invited to participate in the study. The past medical and ocular history, visual symptoms, and the results of a full ophthalmological assessment performed 3 months after starting treatment were noted. Any patient with retinal changes was followed up at 3 month intervals until the changes resolved. RESULTS Of the 25 patients examined, four had evidence of retinopathy including deep retinal haemorrhage and cotton wool spots. Two of the patients were diabetic and one hypertensive. None had any visual symptoms and in all four the retinopathy resolved while the patients completed their course of treatment. CONCLUSIONS The incidence of retinopathy with pegylated interferon is low. The retinal complications resolve while treatment is continued and are asymptomatic. This study does not support routine screening for retinopathy in patients treated with pegylated interferon and ribavirin for hepatitis C.
Collapse
Affiliation(s)
- F M Cuthbertson
- St James University Hospital, Beckett Street, Leeds LS9 7TF, UK.
| | | | | |
Collapse
|
|
22
|
Crochet M, Ingster-Moati I, Even G, Dupuy P. Rétinopathie à l’interféron-α associé à la ribavirine : atteinte de l’électro-oculogramme. J Fr Ophtalmol 2004; 27:257-62. [PMID: 15039627 DOI: 10.1016/s0181-5512(04)96127-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
AIM Ophthalmological complications with interferon alpha (INF-alpha) have been described since 1992: toxic retinopathy with cotton-wool spots, retinal hemorrhages, visual evoked potential (VEP) modifications and visual field abnormalities. MATERIAL AND METHOD In 2002, a 44-year-old woman was referred complaining of visual problems. In 1986, she had been diagnosed with chronic hepatitis C and underwent INF-alpha therapy for 6 months with no ophthalmological symptoms. In 2001, she began a second course of INF-alpha therapy along with ribavirin. After 5 months, in February 2002, she developed hypothyroidism induced by INF, received levothyroxine and her treatment for the hepatitis C was stopped. One month later, in March, she complained of visual difficulties in dim light. Clinical ophthalmological examination and Goldmann visual field testing, electroretinogram (ERG) and visual evoked potentials (VEP) were normal but the electro-oculogram (EOG) showed that the light-peak-to-dark-trough ratios were very low: 148% in the right eye, 156% in the left eye. The fluorescein angiography was normal. The patient was followed up 4 months later, in June 2002 (after 5 months without INF-alpha therapy), showing a slight improvement of the EOG and no visual symptoms. Two other follow-up examinations were done in September 2002 and January 2003: the slight improvement persisted but the EOGs remain below the normal range values. DISCUSSION AND CONCLUSION A review of the literature brought out that an EOG is not usually done in the monitoring of patients taking INF-alpha, but we decided to do this examination because of her symptoms, the first case to our knowledge in a patient taking INF-alpha. This case report underlines the necessity of an EOG on patients with INF-alpha therapy. Until now, the pathogenesis of this retinal toxicity has been poorly understood. These results show that the retinal pigmented epithelium is probably implicated at an early stage in this retinal toxicity.
Collapse
|
|
23
|
Current awareness in pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2003; 12:431-46. [PMID: 12899122 DOI: 10.1002/pds.791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
|