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Ocular Complications of Herpes Zoster Ophthalmicus

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Ocular Complications of Herpes Zoster Ophthalmicus UNIVERSITY OF LONDON OCULAR COMPLICATIONS OF HERPES ZOSTER OPHTHALMICUS Approved as the subject for the Degree of Doctor of Medicine by the Faculty of Clinical Medicine, London University 1993 Ronald John Marsh MB.BS.(hons)(London), FRCS (England), FRCOPHTH Training Institutions The Royal London Hospital Medical College Turner Street Whitechapel London El 2AD and Moorfields Eye Hospital City Rd London EC1V 2FD Consultant Ophthalmologist Moorfields Eye Hospital City Road, London, EC1V 2FD & St Mary's Hospital Eye Department (Western Eye Hospital) Marylebone Road London NWI 5YE September 1997 ProQuest Number: U643730 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U643730 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 2 ABSTRACT Fifty percent of patients with ophthalmic zoster develop ocular complications. These may be mild or severe, and can lead to loss of sight which, by timely and good management can be prevented in most cases. Unfortunately knowledge of the complications and their management is often poor making the design and interpretation of clinical trials difficult. 1356 cases of ophthalmic zoster were collected over fifteen years with at least 6 months follow up. Their details and complications were entered into a database. There is a generally held impression that patients developing zoster do so because of impaired immunity. Analysis of our findings showed that this was not so. The database results were analyzed to quantify the incidence of complications and their correlates. Two common corneal complications that are difficult to manage and lead to visual impairment were studied in detail including: Mucous plaque keratitis is defined as a distinct entity appearing at an early or late stage and occurred in forty seven cases. Poor management leads to visual impairment from neurotrophic ulceration, megaplaque keratitis and glaucoma. Lipid keratopathy induces diminished visual acuity and photophobia. It occurred in thirty six cases. Careful and prolonged treatment of chronic stromal keratitis with topical steroid will prevent this occurring, but when it does successful laser occlusion of corneal blood vessels halts the deposition of lipid and may actually disperse it or make the host cornea safer for keratoplasty. One hundred and seventy six patients were screened orthoptically and the incidence of extraocuiar muscle palsies assessed with regard to distribution and natural history. Possible pathogeneses are discussed. Overall recovery was good. Lastly iritis and iris atrophy were identified in five hundred and twenty patients and twenty three were investigated with anterior segment fluorescein angiography. This showed that they were associated with an ischaemic vasculitis. CONTENTS 1 ABSTRACT 2 ERRATA AND CORRIGENDA 10 ACKNOWLEDGEMENTS 11 GLOSSARY OF TERMS 13 2 INTRODUCTION 14 2.1 The Problem 14 2.2 Scope of inquiry 14 2.21 The incidence of clinical impairments inimmunity 14 2.22 The incidence and correlations of ocular complications 1 5 2.23 The natural history and management 15 of the following corneal complications. 2.23a Mucous plaque keratitis 15 2.23c Lipid keratopathy 15 2.24 External oculomotor palsies in zoster 15 2.25 Iris angiography in zoster with iritis and iris atrophy 15 3 HISTORICAL REVIEW OF THE LITERATURE 1 7 3.01 Virology 17 3.02 Epidemiology 18 3.03 Immunology 19 3.03a Humoral im m unity 19 3.03b Ceiiuiar immunity 20 3.04 Aetiology 21 3.05 General Pathogenesis 21 3.05a Latency 21 3.05b Reactivation 22 3.05b1 Reduced immunity 22 3.05b2 Trauma 22 3.05b3 Other factors 23 3.05b4 Aging 23 3.06 Pathogenesis of eye disease 24 3.07 Histopathology 24 3.07a Trigeminal ganglion 25 3.07b Brain 25 3.07c Peripheral nerves 25 3.07d Orbit 25 3.07e Globe 25 3.1 GENERAL CLINICAL FEATURES 26 3.10 Onset 26 3.11 Age and Sex distribution 26 3.12 Rash 26 3.13 Systemic Involvement 27 3.14 Investigation 27 OCULAR AND NEUROLOGICAL FEATURES 3.2 Ocular and Neurological Features 27 3.20 Acute Ocular lesions 28 3.3 ACUTE NEUROLOGICAL LESIONS 33 3.4 CHRONIC OCULAR LESIONS 35 3.4a Mucous plague keratitis 35 3.4b Diffuse Eoitheliooathv 36 3.4c Lipid Keratopathv 37 3.5 CHRONIC NEUROLOGICAL LESIONS 37 3.6 RECURRENT DISEASE 38 3.7 TREATMENT 39 3.70 Systemic Therapy 39 3.8 SPECIFIC TREATMENT 43 3.80 Skin Treatment 43 3.80c Topical Management o f Postherpetic Neuralgia 43 3.81 Lid Treatment 44 3.82 OCULAR THERAPY 44 3.83 Management of neurotrophic keratitis 46 3.84 SURGERY 47 3.85 SUMMARY 48 4 METHOD USED FOR EXPLORING THE PROBLEMS 49 4.1 Clinical Setting 49 4.2 Patient Selection 49 4.3 History & Standard Examination 49 4.4 Additional Examinations 49 4.41 Measurement of corneal sensation 50 4.42 Transpupillary transillumination. 50 4.43 Corneal and iris fluorescein angiography 50 4.5 General Recording of information 50 4.6 Selection of patients for the different studies 51 5 THE PREVALENCE OF CLINICAL IMPAIRMENTS IN IMMUNITY 52 5.1 Introduction 52 5.2 Patients and methods 52 5.3 Results 52 5.4 Discussion 54 6 THE INCIDENCE OF OCULAR COMPLICATIONS IN OPHTHALMIC ZOSTER, THEIR CORRELATIONS AND SUPPLEMENTARY NOTES ON SOME COMPLICATIONS 56 6.1 Introduction 56 6.2 Methods 56 6.3 Results 56 6.34 OCULAR COMPLICATIONS 57 6.34a Corneal Complications 59 6.34a1 Neurotrophic keratitis 60 6.34a2 Diffuse epitheliopathy 62 6.34a3 Megaplaque keratitis 63 6.34b Retinal pigment epithelial degeneration 64 6.35 NEUROLOGICAL COMPLICATIONS 64 6.36 CORRELATIONS 64 6.37 NO CORRELATIONS 66 6.4 Discussion 68 6.41 Comparison with other series 69 7 CORNEAL MUCOUS PLAQUE KERATITIS 70 7.1 Introduction 70 7.2 Patients and methods 71 7.3 Results 71 7.30 Associated clinical features 73 7.31 Differentiating features 76 7.4 Discussion 77 7.41 Pathogenesis 79 8 LASER TREATMENT OF LIPID KERATOPATHY IN ZOSTER 80 8.1 Introduction 80 8.2 Patients and Methods 82 8.3 Results 86 8.30 Complications 89 8.4 Discussion 89 8.40 Pathogenesis 91 9 OCULAR PALSIES (Natural History, Management & Pathogenesis) 92 9.1 Introduction 92 9.2 Patients and Methods 92 9.3 Results 92 9.4 Discussion 96 9.41 Pathogenesis 97 9.42 Treatment 99 10 IRIS ANGIOGRAPHY IN ZOSTER WITH IRITIS AND IRIS ATROPHY 100 10.1 Introduction 100 10.2 Patients and Methods 100 10.20 Iris angiography 101 10.3 Results 101 10.30 Normal iris angiograph y 101 10.31 Angiographic findings in herpes zoster uveitis 102 10.31b Herpes zoster iris atrophy 105 10.32 Herpes Simplex uveitis 105 10.4 Discussion 107 10.40 Pathogenesis 107 10.41 Differential Diagnosis 107 10.42 Treatment 107 11 APPENDIX 109 A Proforma for recording types and severity of 110 ocular complications B Proforma for treatment of lipid keratopathy 111 12 DISCUSSION AND 112 CONCLUSIONS 13 REFERENCES 122 FIGURES 6.1 Age and sex distribution of ophthalmic zoster 56 6.2 Correlation between severity of the rash and neuralgia 57 6.3 Incidence and severity of episcleritis/scleritis and iritis 59 6.4 Incidence of different types of keratitis 60 6.5 Typical neurotrophic ulcer 60 6.6 Megaplaque keratitis 63 6.7 The relations between early and late neuralgia corneal sensation and age 64 7.1 Mucous plaque keratitis stained with Rose Bengal 70 7.2 The age distribution of MPK patients compared with overall 72 7.3 The variation in time of onset of MPK 73 7.4 Duration of Mucous Plaque Keratitis 73 8.1 Eccentric type of lipid keratopathy 84 8.2 Fluorescein angiography of cornea above 84 8.3 Disciform type of keratopathy 88 8.4 Same patient as above 3 years after start of laser treatment 88 9.1 Distribution of nerve involvement in external ocular palsies 93 9.2 Histogram of age distribution in zoster 94 9.3 Histogram of duration of diplopia in ophthalmic zoster 95 10.1 Normal iris angiogram 102 10.2 Iris angiogram in early iritis 102 10.3 Early sectoral iris atrophy in herpes zoster 104 10.4 Fluorescein angiogram of iris atrophy shown above 104 10.5 Iris atrophy in herpes simplex. 106 10.6 Fluorescein angiogram of iris atrophy shown above. 106 TABLES 4.1 Special history and examination 49 5.1 The prevalence of preceding systemic disease 53 in 1000 patients with HZO 5.2 Haematology results in 364 patients with abnormal investigations 54 6.1 The number of different complications seen 58 6.2 Correlations between iritis and the severity of the rash 65 6.3 Correlations between severity of the rash and 66 neurotrophic keratitis 6.4 Correlations between diminution of corneal sensation 66 and MPK 6.5 Comparisons of the incidence of ocular complications in different series 67 7.1 Incidence of associated clinical features occurring before and simultaneously with MPK. 74 7.2 Incidence of clinical features following MPK 75 7.3 Numbers of patients with decreased visual acuity 75 7.4 Cases requiring surgery 77 8.1 Effect of laser on the extent of opacity 87 8.2 Effect of treatment on the density of opacities 87 8.3 Effect of laser treatment on visual acuity 87 9.1 Laterality of external ocular palsy 93 9.2 Ipsilateral palsies becoming contralateral 94 9.3 The association of ocular palsies with other complications 96 ERRATA & CORRIGENDA 10 ACKNOWLEDGEMENTS 6.6 Co-workers: Over the years a succession of doctors helped me in the clinic for variable periods of time, the minimum being a year.
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