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Preface

Dr. Sainz de la Maza published the ﬁrst edition of this text on the sclera over 18 years ago, as a consequence of Dr. Sainz de la Maza being unable to ﬁnd a copy of a monograph on the subject by Dr. Hazleman and Mr. Watson upon her return to Spain after her fellowship in Boston with me in Ocular Immunology and Uveitis. She had fallen in love with my copy of that book, and was stunned and depressed when she discovered that it was out of print and that none of the libraries in Barcelona possessed a copy of the book. Cunning catalan that she is, she connived to obtain a Fulbright scholarship to return to Boston for another year of fellowship with me, with the prime objective of exploiting my collection of patients with scleritis (and me) for the production of a book on the sclera. The text turned out to be a huge success, selling out, and hence the invitation from Springer Verlag was forthcoming for us to produce a second edition of this work. It has been a pleasure to work once more with Dr. Sainz de la Maza on this project, producing this updated work on a subject which is widely neglected and for which, therefore, there is need for such a work.

The sclera composes 80% of the geographic extent of the exterior conﬁnes or wall of the eyeball, yet it receives relatively little attention in the ophthalmic literature. This is understandable, given the fact that disorders of the sclera are not common and the fact that, when relatively minor problems of the sclera do develop, healing without consequence is the usual outcome. After all, a scar in the sclera is of little importance, because the sclera is an opaque structure. Such a scar in the cornea, or an opacity in the lens or vitreous, or a scar in the macula, of course, carries inﬁnitely more visual signiﬁcance. But it is exactly this rarity of signiﬁcant sclera problems, coupled with the profound systemic implications that some inﬂammatory disorders of the sclera carry, that makes studies of the sclera and its disorders important. Indeed, a substantial proportion of individuals who develop serious sclera inﬂammation are discovered to have an occult systemic disease; in The Sclera and Systemic Disorders, Watson and Hazleman1 emphasized that 27% of patients who develop necrotizing scleritis are dead within 5 years from a systemic, vasculitic lesion. Watson and Hazleman also emphasized that because of the comparative rarity of sclera disease, the diagnosis is often

1 Watson PG, Hazleman BL: The Sclera and Systemic Disorders, WB Saunders, Philadelphia, 1976.

vii

viii	Preface

missed, and 40% of eyes reported in one series of enucleated eyes had had a primary diagnosis of scleritis.

We began with all that we had learned from Watson and Hazleman and built on that excellent foundation. The basis of our current experience springs from the Massachusetts Eye Research and Surgery Institution (MERSI) in Cambridge, Massachusetts, and from the Hospital Clinic of Barcelona, Spain, dating from 2005, both devoted to the study and care of patients with any inﬂammatory problem related to the eye, from the lids to the optic nerve. The ﬁrst Research Fellow joined the service of Dr. Foster in 1980, and the ﬁrst Clinical Fellow arrived in 1984. Between 1977 and 2011 approximately 150,000 patient visits have occurred, approximately 10,000 new patients have been evaluated, and 110 Ocular Immunology Fellows have been trained in the service. Dr. Sainz de la Maza was one of those Fellows, and in the course of training she developed a special interest in and afﬁnity for patients with scleritis. It was her initiative that was at the heart of the genesis of this project, and it is entirely through her efforts that this project has been successfully completed.

Our hope is that this book will serve as a resource for residents in ophthalmology, for cornea and immunology fellows in training, and for those ophthalmologists in practice and on faculties who have an interest in patients with diseases of the sclera. The majority of the book is devoted to sclera inﬂammation because scleritis represents, by far, the most common sclera disorder encountered in ophthalmic practice, and because of the profound systemic implications of scleritis. The references at the end of each chapter, although not exhaustive, are generous in number and should provide the reader with more than enough original source material for further reading. Finally, we would enthusiastically encourage you to read the book The Sclera and Systemic Disorders, second edition2 as well as this one.

Cambridge, MA, USA

C. Stephen Foster

2 Watson PG, Hazleman BL, Pavesio CE, Green WR: The Sclera and Systemic Disorders, Elsevier Limited, Philadelphia, 2004.

1 Structural Considerations of the Sclera.......................................			1
1.1	Introduction.............................................................................		1
1.2	Development of the Sclera......................................................		1
	1.2.1 Prenatal Development: Ultrastructural Studies ...........		1
	1.2.2	Prenatal Development: Immunohistochemical
		Studies .........................................................................	7
	1.2.3 Postnatal Development and Age-Related
		Changes .......................................................................	8
1.3	Anatomy..................................................................................		9
	1.3.1 Gross and Microscopic Anatomy ................................		9
	1.3.2	Ultramicroscopic Anatomy .........................................	19
1.4	Biochemistry ...........................................................................		22
1.5	Immunohistochemistry ...........................................................		22
1.6	Biomechanics..........................................................................		23
1.7	Molecular Structure ................................................................		23
	1.7.1	Collagen .......................................................................	23
	1.7.2	Elastin ..........................................................................	24
	1.7.3	Proteoglycans ..............................................................	24
	1.7.4	Glycoproteins ..............................................................	25
	1.7.5	Matrix - Degrading Enzymes ........................................	25
	1.7.6	Fibroblast Growth Regulation .....................................	26
1.8	Summary .................................................................................		26
References		........................................................................................	27
2 Immunologic ..................................Considerations of the Sclera			31
2.1	General ............................Immune Response Considerations		32
	2.1.1 .........Components of the Adaptive Immune Response		32
	2.1.2 .......................................................	Immunoregulation	40
	2.1.3 .....................Abnormalities of the Immune Response		41
2.2	Connective ........................Tissue and the Immune Response		45
	2.2.1 .........Fibroblast Functions and the Immune Response		45
2.3	The Sclera .....................and the Immune Response: Scleritis		46
	2.3.1 ..........................Immune Characteristics of the Sclera		46
	2.3.2 ......................The Susceptible Host: Immunogenetics		46

x			Contents

	2.3.3	Etiology .......................................................................	47
	2.3.4	Pathogenesis ................................................................	49
2.4	Summary .................................................................................		50
References........................................................................................			51
3 Diagnostic Approach of Episcleritis and Scleritis.......................			57
3.1 Investigation of the Illness ......................................................			58
	3.1.1 Major Complaint and History of Present Illness .........		59
	3.1.2	Past History..................................................................	60
	3.1.3	Family History.............................................................	60
	3.1.4 Past and Present Therapy History................................		60
	3.1.5	Review of Systems ......................................................	60
	3.1.6	Systemic Examination .................................................	62
	3.1.7	Ocular Examination.....................................................	64
3.2	Diagnostic Tests ......................................................................		71
	3.2.1	Blood Tests ..................................................................	71
	3.2.2 Anterior Chamber Polymerase Chain
		Reaction Testing ..........................................................	79
	3.2.3	Smears and Cultures ....................................................	79
	3.2.4	Skin Testing .................................................................	80
	3.2.5	Radiologic Studies.......................................................	80
	3.2.6 Anterior Segment Fluorescein Angiography...............		80
	3.2.7 Anterior Segment Indocyanine Green Angiography ...		84
	3.2.8	Other Imaging Studies.................................................	85
3.3	Biopsy	.....................................................................................	88
	3.3.1 Biopsy for Suspected Systemic
		Vasculitic Disease........................................................	88
	3.3.2 Biopsy for Suspected Local or Systemic
		Infectious Disease........................................................	89
3.4	Data Integration: Diagnosis ....................................................		89
3.5	Therapeutic Plan .....................................................................		89
3.6	Summary .................................................................................		89
References........................................................................................			90
4 Clinical Considerations of Episcleritis and Scleritis...................			95
4.1	Episcleritis...............................................................................		96
	4.1.1	Introduction .................................................................	96
	4.1.2	Patient Characteristics .................................................	96
	4.1.3	Clinical Manifestations................................................	97
	4.1.4	Classiﬁcation of Episcleritis ........................................	99
	4.1.5	Associated Diseases.....................................................	100
	4.1.6	Precipitating Factors ....................................................	100
4.2	Scleritis ...................................................................................		102
	4.2.1	Introduction .................................................................	102
	4.2.2	Patient Characteristics .................................................	102
	4.2.3	Clinical Manifestations................................................	102
	4.2.4	Classiﬁcation ...............................................................	105

Contents				xi

		4.2.5	Associated Diseases.....................................................	125
		4.2.6	Complications of Scleritis ...........................................	126
	4.3	Summary .................................................................................		132
	References........................................................................................			133
5	Pathology in Scleritis .....................................................................			137
	5.1 General Considerations of Connective Tissue
		Inﬂammation ...........................................................................		137
		5.1.1	Chronic Nongranulomatous Inﬂammation ..................	138
		5.1.2	Chronic Granulomatous Inﬂammation ........................	138
		5.1.3	Fibrinoid Necrosis .......................................................	138
		5.1.4	Vascular Inﬂammation.................................................	139
	5.2 Speciﬁc Considerations of Scleral Tissue Inﬂammation ........			139
		5.2.1	Pathology of Episcleritis..............................................	141
		5.2.2	Pathology of Scleritis...................................................	141
	5.3	Biopsy	.....................................................................................	164
		5.3.1	Noninfectious Necrotizing Scleritis ..........................	164
		5.3.2	Noninfectious Recurrent Diffuse or Nodular
			(Nonnecrotizing) Scleritis .........................................	164
		5.3.3	Infectious Scleritis (Diffuse, Nodular,
			or Necrotizing Scleritis) ............................................	165
		5.3.4	Biopsy Technique ......................................................	165
	5.4	Summary .................................................................................		166
	References........................................................................................			167
6	Noninfectious Scleritis ...................................................................			173
	6.1 Systemic Immune-Mediated Disease-Associated Scleritis:
		Vasculitides .............................................................................		174
		6.1.1	Adult Rheumatoid Arthritis.......................................	174
		6.1.2	Systemic Lupus Erythematosus ................................	189
		6.1.3	Ankylosing Spondylitis .............................................	194
		6.1.4	Reactive Arthritis (Reiter) .........................................	199
		6.1.5	Psoriatic Arthritis ......................................................	203
		6.1.6	Inﬂammatory Bowel Disease-Associated
			Arthritis .....................................................................	206
		6.1.7	Relapsing Polychondritis...........................................	208
		6.1.8	Polyarteritis Nodosa ..................................................	211
		6.1.9	Allergic Granulomatous Angiitis (Churg–Strauss
			Syndrome) .................................................................	213
		6.1.10	Granulomatosis with Polyangiitis (Wegener)............	214
		6.1.11	Adamantiades–Behçet’s Disease...............................	217
		6.1.12	Giant-Cell Arteritis....................................................	220
		6.1.13	Cogan’s Syndrome ....................................................	222
		6.1.14	Systemic Immune-Mediated Diseases Associated
			with Scleritis: Atopy..................................................	223
		6.1.15	Other Systemic Immune-Mediated Diseases
			That Rarely May Be Associated with Scleritis
			and Episcleritis ..........................................................	224
		6.1.16	Systemic Immune-Mediated Disease-Associated
			Scleritis After Ocular Surgery...................................	225

xii			Contents

6.2	Dermatological Disease-Associated Scleritis .........................		226
	6.2.1	Rosacea ........................................................................	226
6.3	Metabolic Disease-Associated Scleritis..................................		226
	6.3.1	Gout .............................................................................	226
6.4	Foreign Body Granuloma-Associated Scleritis ......................		227
6.5	Chemical Injury-Associated Scleritis .....................................		227
6.6	Summary .................................................................................		228
References		........................................................................................	228
7 Infectious ..........................................................................Scleritis			241
7.1	Bacterial ....................................................................Scleritis		242
	7.1.1 Gram-Positive Coccus and Gram-Negative
	................................................................	Rod Scleritis	242
	7.1.2 ................................................	Mycobacterial Scleritis	245
	7.1.3 .....................................................	Spirochetal Scleritis	250
	7.1.4 ....................................................	Chlamydial Scleritis	254
	7.1.5 ...............................................	Actinomycetic Scleritis	254
7.2	Fungal .......................................................................Scleritis		255
	7.2.1 ..............Filamentous and Dimorphic Fungal Scleritis		255
7.3	Viral ..........................................................................Scleritis		258
	7.3.1 ............................................................	Herpes Scleritis	258
	7.3.2 ...........................................................	Mumps Scleritis	265
7.4	Parasitic .....................................................................Scleritis		265
	7.4.1 ........................................................	Protozoal Scleritis	266
	7.4.2 .....................................................	Helminthic Scleritis	268
7.5	Summary .................................................................................		269
References........................................................................................			270
8 Noninﬂammatory ......................................Diseases of the Sclera			277
8.1	Scleral ......................................................................Deposits		277
	8.1.1 ...........................................	Scleral Protein Deposition	277
	8.1.2 ..............................................	Scleral Lipid Deposition	281
	8.1.3 .................................	Scleral Carbohydrate Deposition	281
	8.1.4 ..........................Scleral Mineral Deposition: Calcium		281
	8.1.5 .........................Scleral Pigment Deposition: Bilirubin		282
8.2	Scleral ..............................................Thinning (Blue Sclerae)		283
	8.2.1 Scleral Thinning in Inherited or Congenital
	.......................................................................	Diseases	283
	8.2.2 .......................Scleral Thinning in Acquired Diseases		286
8.3	Scleral ..................................................................Thickening		287
	8.3.1 ............................................................	Nanophthalmos	287
	8.3.2 ...........................................................	Scleropachynsis	287
	8.3.3 ...............................................................	Phthisis Bulbi	287
8.4	Scleral ........................................................................Tumors		288
	8.4.1 ..................................................	Dermoid Choristomas	288
	8.4.2 ........................................................	Epithelial Tumors	288
	8.4.3 ................................Dense Connective Tissue Tumors		289
	8.4.4 ..........................................................	Vascular Tumors	289
	8.4.5 ......................................................	Blood Cell Tumors	290

Contents			xiii

	8.4.6	Nervous Tumors ..........................................................	290
	8.4.7	Pigmented Tumors .......................................................	291
	8.4.8	Secondary Tumors .......................................................	292
8.5	Summary .................................................................................		292
References		........................................................................................	292
9 Treatment of Episcleritis and Scleritis .........................................			299
9.1	Treatment .........................................................of Episcleritis		299
9.2	Treatment ..............................................................of Scleritis		300
	9.2.1 .......................................................	Medical Treatment	300
	9.2.2 ........................................................	Ancillary Therapy	304
	9.2.3 ...............................	Drug Management Responsibility	304
	9.2.4 .......................................................	Surgical Treatment	305
9.3	Summary .................................................................................		307
References........................................................................................			307
Index......................................................................................................			309

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Preface

Contents