S E C T I O N

31 Sclera

345 EPISCLERITIS 379.00

Peter G. Watson, MA, MBBChir, FRCS, FRCOphth, DO

Cambridge, England

Episcleritis is a benign, recurrent, self-limiting inflammation of the highly vascularized episclera which is closely attached to the underlying sclera and the mobile Tenon’s capsule. It is contiguous with the fascial coats of the extraocular muscles. As neither the conjunctiva above nor the sclera below is involved in the inflammatory process, episcleritis does not threaten the vision or anatomical integrity of the eye.

The etiology of episcleral disease is unknown, but with the exception of children below 12 years of age, almost all patients who have an associated systemic disease – often gout, rosacea or connective tissue disorder are in the older age group, whereas those who have evidence of hypersensitivity reactions or migraine are in the younger group. Episcleritis with onset before puberty usually ceases at puberty; episcleritis starting before the menopause usually ceases with menopause. However, no hormonal abnormalities have ever been demonstrated. There is no genetic predisposition to episcleritis.

Clinically there are two ill defined and overlapping groups of patients. The first group is younger, between 13 months and 60 years old. These patients have an acute onset and a rapid benign course with recurrences over a period of 1 month to 3 years. The second group of patients, age 40 to 80, have less severe inflammation but a much longer course. More than half of patients with episcleritis have intermittent attacks that usually continue for 3 to 6 years, although some patients have had attacks for as long as been known to go on for up to 30 years.

The onset is sudden and unpredictable and may or may not be accompanied by pain or discomfort. The pain is localized to the eye and does not radiate to the face or jaw. Attacks last between 7 to 10 days, whether treated or not, and have a strong tendency to recur either at the same site or elsewhere in the same or opposite eye.

DIAGNOSIS

Episcleritis may be simple (diffuse) or nodular. Simple episcleritis accounts for 75% of cases, nodular episcleritis for the remainder. Both varieties are twice as common in women as men.

Clinical signs and symptoms

In simple episcleritis the onset is sudden. Pateints report discomfort, a pricking sensation, and some swelling around the

eyes. The affected eye can be intensely red and watery but there is never any purulent discharge. The inflammation may cover part of the anterior episclera or the whole globe. Involvement of the posterior episclera and muscle fascia may result in minor transient diplopia.

In nodular episcleritis the inflammation remains localised to one place and recurrences are generally at the same location. The onset is less acute and resolution is slower in nodular disease. Some of the nodules can be very large but there are no residual structural abnormalities in the episcleral tissue or the sclera.

In both simple and nodular episcleritis, anterior segment angiography reveals a very rapid circulation time with transudation of fluid resulting from increased permeability of vessels.

In those patients who develop episcleritis as a result of migraine there is temporary localised vascular closure of pre capillary arterioles. In all varieties the vascular pattern remains normal and does not become distorted or rearranged as in scleral disease.

The diagnosis of episcleritis is through the history and the clinical observation of the depth and extent of the inflammation. No specific laboratory investigations are available. Seven percent of patients have hyperuricemia even in the absence of clinical gout and 15% have serological indicators of connective tissue disease. Episcleritis may be the first sign of a systemic connective tissue disorder. Children under the age of 12 years with episcleritis have a high incidence of systemic disease or viral infection.

TREATMENT

As episcleritis is self limiting and causes no permanent damage to the eye it does not usually require treatment. However, treatment is appropriate on the first attack or if the inflammation or discomfort is particularly severe. Therapy reduces patient discomfort but does not affect the duration of the inflammation.

First attack of episcleritis

A careful history is required to rule out the possibility of any intercurrent disease. If any is present, including migraine, this should be treated appropriately, immediately and vigorously. Vigorous, focused treatment at this stage often eliminates recurrences.

In the active phase of inflammation (within 48 hours of onset) offer topical prednisolone 0.5% administered every 30 minutes during the day and on waking at night. The dose is then reduced to 4 times daily for 2 days, twice the next day and once daily for the next 2 days. If prednisolone treatment is

Sclera • 31 SECTION

introduced the therapy should continue over the full course. If withdrawn early, rebound inflammation frequently occurs.

If the episcleritis is first seen after 48 hours no treatment other than cold artificial tears and cold compresses should be prescribed.

Recurrent episcleritis

Treat initially with cold compresses and artificial tears. However, if the inflammation is severe and disabling a systemic NSAID should be prescribed such as flubiprofen 100 mg 3 times a day, or its equivalent. COX II inhibitors do not appear to be as effective as NSAIDs, but as patients responses can be idiosyncratic, different preparations should be tried as some patients will respond to one compound but not another.

PRECAUTIONS

Long term, continuous local corticosteroid therapy should not be administered because of the danger of inducing cataract and glaucoma.

REFERENCES

Foster CS, Sainz de la Maza M: The sclera. New York, Springer-Verlag, 1993.

Read RW, Weiss AG, Sherry D: Episcleritis in childhood. Ophthalmology 106:2377–2379, 1999.

Watson PG, Hayreh SS: Scleritis and episcleritis. Br J Ophthalmol 60:163– 191, 1976.

Watson PG, Hazleman BL, Pavesio C, Green WR: The sclera and systemic disorders. 2nd edn. New York, Butterworth-Heinemann, 2004.

346 SCLERAL STAPHYLOMAS

AND DEHISCENCES 379.11

Bishara M. Faris, MD, FACS

Worcester, Massachusetts

H. Mackenzie Freeman, MD

Boston, Massachusetts

Localized weakening of the sclera may lead to formation of a thin oval or elliptic area through which the choroid is visible. When flat and meridionally oriented, such areas are termed scleral dehiscences; they are referred to as staphylomas when they are bulging.

ETIOLOGY/INCIDENCE

Staphylomas may be congenital or acquired. They are classified as anterior or posterior, depending on their relationship to the equator of the eye.

●Posterior staphylomas are found in patients with myopia of great than -8 diopters (D) as well as in patients with the connective tissue disorders of Ehlers–Danlos and Marfan syndromes.

●Anterior staphylomas are common operative findings among patients with nontraumatic rhegmatogenous retinal detachment, with a reported incidence of 14%. Less commonly,

they occur in eyes with increased intraocular pressure and recurrent necrotizing scleritis and after deep scleral resection for episcleral malignancies. Anterior staphylomas also have been reported after subconjunctival injections of corticosteroids and in patients with neurofibromatosis and sarcoidosis.

COURSE/PROGNOSIS

Staphylomas may progress with patient age. The progression of posterior staphylomas causes increasing chorioretinal degeneration and breaks in Bruch’s membrane, which may result in subsequent growth of neovascular membranes and subretinal bleeding.

Posterior staphylomas may contribute to the development of macular hole formation and retinal detachment.

DIAGNOSIS

●Anterior staphylomas are seen through the bulbar conjunctiva as areas of bluish discoloration of the thin sclera.

●Posterior staphylomas can be seen best with indirect ophthalmoscopy. The thinned sclera bulges posteriorly and is lined by a thin and atrophic choroid. The size and location of these lesions can be accurately determined using ophthalmic B-scan ultrasound and computed tomography (CT) scan.

PROPHYLAXIS

Rupture of the globe may complicate scleral dehiscences and staphylomas. Extraocular muscles in the large staphylomatous globes are commonly thin. During strabismus surgery on such eyes and when scleral bites are taken, scleral perforation may result.

Scleral perforation may also occur when local anesthetics are administered to eyeballs with staphylomas in preparation for intraor extraocular surgery. Hence, periocular infiltration is mandatory in patients with posterior staphylomas and retrobulbar infiltration in patients with anterior staphylomas.

In planning for retinal detachment surgery, that a history of staphyloma in one eye should alert the surgeon to the possibility of its occurrence in the fellow eye.

TREATMENT

Supportive

A sustained elevation of intraocular pressure, especially in children, may result in formation of anterior scleral dehiscences or staphyloma, so lowering pressure by carbonic anhydrase inhibitors, adrenergics, beta-adrenergic blocking agents, alpha agonists, prostaglandins, or miotics is in order. Forceful rubbing of the eyeballs produces a marked elevation in pressure and should be avoided.

Surgical

During surgery for retinal detachment

When dehiscences and staphylomas are discovered in the area to be buckled during retinal detachment surgery, certain opera-

tive precautions should be taken to prevent accidental rupture of the globe. In localizing the retinal breaks, the indentation should be performed using a cotton-tipped applicator rather than a metal electrode. The blunt edges of the implant should extend over thin scleral zones and end on healthy sclera. When applying cryoapplications, the cryoprobe tip should be applied gently and should not be removed until it has completely thawed. Premature probe movements may rupture the sclera.

The assistant surgeon has an important role to play during surgery. Gentle exposure of the globe prevents sudden increases in intraocular pressure and subsequent rupture of the globe. It may be safer to detach more rectus muscles to obtain good exposure of the surgical field than to resort to forceful exposure.

The use of intravenous acetazolamide and mannitol to lower the intraocular pressure and minimize the risk of globe rupture is advised in all cases, unless there is a medical contraindication. Paracentesis may be used as a last resort when intravenous medications fail to lower the eye pressure adequately.

Our recommended procedure is pars plana vitrectomy, internal drainage with endophotocoagulation, and air-gas exchange.

During surgery for episcleral malignancies

Scleral resection is done whenever there is evidence of scleral involvement. Deep resections involving two-thirds or more of the scleral thickness may predispose a patient to the formation of dehiscences and staphylomas. In such cases, it is wise to cover the resected zones with a preserved scleral graft or an autogenous pretibial periosteal patch graft.

Surgical reinforcement of posterior staphylomas using donor sclera, silicone rubber, or fascia lata has been performed in countries outside the United States. No controlled studies have been made to document the benefits of such procedures.

COMMENTS

Anterior scleral staphylomas are most often located in the superior temporal quadrants. Hence, these quadrants should be avoided when subconjunctival injections of antibiotics and corticosteroids are indicated. Preoperative inspection of these quadrants is mandatory when retinal detachment occurs in myopic eyes. When staphylomas are encountered during retinal detachment surgery, they can be the site of rupture of the globe unless specific operative measures are taken.

REFERENCES

Coroneo MT, Beaumont JT, Hollows FC: Scleral reinforcement in the treatment of pathologic myopia. Aust N Z J Ophthalmol 16:317–320, 1988.

Faris B, Freeman HM, Schepens CL: Scleral dehiscences, anterior staphyloma and retinal detachments-Part 1: incidence and pathogenesis. Trans Am Acad Ophthalmol Otolaryngol 79:851–853, 1975.

Freeman HM, Schepens CL, Faris B: Scleral dehiscences, anterior staphyloma, and retinal detachment-Part 2: surgical management. Trans Am Acad Ophthalmol Otolaryngol 79:854–857, 1975.

Ripandelli G, Parisi V, Friberg TR, et al: Retinal detachment associated with macular hole in high myopia: using the vitreous anatomy to optimize the surgical approach. Ophthalmology 111(4):726–31, 2004.

Sasoh M, Yoshida S, Ito Y, et al: Macular buckling for retinal detachment due to macular hole in highly myopic eyes with posterior staphyloma. Retina 20(5):445–449, 2000.

347 SCLERITIS 379.00

Sinan Tatlipinar, MD

Baltimore, Maryland

Ozge Ilhan-Sarac, MD

Baltimore, Maryland

Esen Karamürsel Akpek, MD

Baltimore, Maryland

Scleritis is an inflammatory disorder of the sclera and deep episclera often associated with vision-threatening ocular complications. Approximately 40% to 50% of patients with scleritis have an identifiable underlying disease. Importantly, scleritis can be the initial manifestation of these disorders. Morbidity in patients with scleritis is primarily based on vasculitis and microangiopathy, suggesting that it is part of an immune complex reaction caused by the interaction of genetic, environmental and endogenous factors. Early diagnosis of scleritis and the underlying disease and the initiation of appropriate systemic therapy can control the progression of the active vasculitic process. Without treatment, the disease course is generally destructive and potentially life threatening. Therefore, it is essential to understand the exact nature of the disease.

EPIDEMIOLOGY/INCIDENCE

Current estimates suggests that the prevalence of scleritis ranges from 0.08% to 4% in the general population. However, the disease may be more common than is currently recognized because of misdiagnoses. Scleritis is generally a disease of middle-aged populations, with a peak of presentation in the fifth decade (age range 11 to 87 years). Most series report a slight female predilection, with a female to male ratio of approximately 1.6 : 1. There is no known racial or geographical predisposition.

COURSE/PROGNOSIS

Scleritis is classified based on the site of pathology and severity of inflammation (Box 347.1). This classification is a useful predictor of the disease course and prognosis as well as a guide to therapy. Scleritis is traditionally divided into anterior (94%) and posterior (6%) types (Box 347.1). Depending on clinical appearance, anterior scleritis is further divided into subtypes such as diffuse, nodular, necrotizing (necrotizing with inflammation) and scleromalacia perforans (necrotizing without inflammation).

Diffuse anterior scleritis is the most common type of scleritis, followed by, in order of frequency: nodular, necrotizing with inflammation, posterior scleritis, and scleromalacia perforans.

The type of scleritis and the severity of inflammation are largely related to the underlying systemic disease. Patients with Wegener’s granulomatosis are more likely to have necrotizing scleritis with peripheral corneal involvement, whereas patients with seronegative spondyloarthropathies tend to have more benign inflammation. Patients with rheumatoid arthritis or relapsing polychondritis usually have disease of intermediate severity.

347 CHAPTER Scleritis •

Sclera • 31 SECTION

BOX 347.1 – Clinical classification of scleritis

Scleritis

Anterior

Diffuse

Nodular

Necrotizing

With inflammation (necrotizing)

Without inflammation (scleromalacia perforans)

Posterior

DIAGNOSIS

Clinical signs and symptoms

Patients with anterior scleritis complain of a gradual onset of deep eye pain radiating to temple, jaw, and sinuses with associated redness, tenderness, lacrimation, and photophobia. Redness is intense with a violaceous hue and may be localized in one sector or the entire sclera. Approximately 34 to 50% of patients have bilateral scleritis.

In diffuse anterior scleritis, the redness is generalized all over the anterior sclera. Slit-lamp examination reveals distortion, tortuosity and congestion of the superficial and deep episcleral plexi with loss of the normal radial pattern (Figure 347.1). When the inflammation disappears, the sclera may appear bluish, mainly because of rearrangement of the collagen fibers, at times with associated thinning.

In the nodular type of anterior scleritis, the hyperemia is localized to one or more areas over scleral nodules that are immobile and extremely tender to touch. Slit-lamp examination reveals congestion and tortuosity of the superficial and deep episcleral plexi overlying the nodules, which are usually localized in the interpalpebral region close to the limbus (Figure 347.2).

Necrotizing scleritis is the most severe and destructive form of scleritis. Patients have more severe pain, which can be provoked by minimal touch to the scalp. On slit-lamp examination white avascular areas surrounded by swelling of the sclera and abnormally congested episcleral vessels can be seen. Without appropriate treatment, these lesions may progress to perforation.

Scleromalacia perforans usually does not cause pain, redness, or clinically apparent inflammation. Yellow or grayish anterior scleral nodules that gradually develop a necrotic slough or sequestrum, eventually separating from the underlying sclera and leaving the choroid bare or covered only by a thin layer of conjunctiva are the characteristic findings of this disorder. Slitlamp examination reveals a reduction in the size and number of the episcleral vessels surrounding the sequestrum, giving a porcelain-like appearance.

Patients with posterior scleritis often present with pain, redness, chemosis, lid edema, lid retraction, proptosis and, most importantly, decreased vision. Exudative retinal detachment, choroidal folds, subretinal mass, vitreitis, disc edema, macular edema, and annular ciliochoroidal detachment may be present. Posterior scleritis is often associated with anterior scleritis. The absence of anterior scleritis makes the diagnosis difficult.

Laboratory findings

Fluorescein angiography of the anterior segment can be used in the diagnosis and reveals early leakage into the extravascular space and venular obstruction. In necrotizing scleritis, arterio-

FIGURE 347.1. Diffuse anterior scleritis with violaceous hue of the underlying sclera and tortuosity of the vasculature.

FIGURE 347.2. A nasal scleral nodule with loss of normal radial pattern of vessels.

lar beading, non-perfused areas and increased transition time and distortion of normal radial pattern of episcleral vessels may be detected. Indocyanine green angiography is also useful, particularly to differentiate episcleritis from scleritis. These two tests provide different and complementary information because each dye has different leakage patterns caused by the difference in optical and chemical properties, and each detects areas of damage not clinically visible.

B-scan ultrasonography is the most useful test in the diagnosis of posterior scleritis. Increased thickness of the sclera and choroid, separation of the posterior surface of the sclera from the episclera, the presence of retinal or choroidal detachments, and swelling of the disc are common findings. Fundus fluorescein angiography is also helpful in the diagnosis of posterior scleritis to detect serous retinal detachment, choroidal folds, retinal striae, and disc and macular edema.

The presence of microangiopathy in most scleritis specimens suggests an underlying Type III hypersensitivity reaction in which the vascular injury is the result of antigen-antibody conjugation within and outside of the vessel wall, with subsequent activation of complement, attraction of neutrophils and fibrinoid necrosis of vessels and surrounding tissue. The antigen is usually the aberrant expression of the HLA-DR on scleral fibroblasts, induced by interferon gamma. Persistent immunologic injury may lead to a chronic response (a type IV hypersensitivity) mediated by epithelioid cells, macrophages,

multinucleated giant cells, and mainly Th1 lymphocytes. This activated immune network, if not treated, leads to scleral destruction.

Differential diagnosis

Diagnosis of scleritis is a clinical one. A painful, intense deep bluish redness or violaceous hue of the sclera is the main sign of anterior scleritis. This is best detected under natural daylight or on penlight examination. Areas of scleral thinning or early necrosis can also be detected with daylight examination. Slitlamp examination with red-free light reveals edema of the sclera and congestion of deep episcleral plexus. White diffuse illumination helps detect abnormal vessels, avascular or necrotic areas, and scleral thinning. The congested deep episcleral vessels are typically not blanched with topically applied 10% phenylephrine.

Approximately half of patients with scleritis have an associated medical condition. A rheumatic disease is seen in about 30–40% of patients. Rheumatoid arthritis (RA) is the most common systemic condition associated with scleritis, seen in 10 to 33% of patients. The majority of these patients (80%) carry a diagnosis of RA at the time of presentation with scleritis. Scleromalacia perforans is almost exclusively associated with rheumatoid arthritis. Systemic vasculitis is the second most common medical condition. About 50% of patients with vasculitis-associated scleritis have Wegener’s granulomatosis. Most importantly, scleritis is the presenting or only clinical finding in a significant proportion of these patients. Systemic lupus erythematosus, relapsing polychondritis, and inflammatory bowel disease are some of the other common rheumatic diseases associated with scleritis.

An infectious etiology, such as herpes zoster, herpes simplex, tuberculosis, syphilis, and Lyme disease, is seen in about 5 to 10% of patients. Herpes zoster is by far the most commonly associated infectious disease.

All patients with scleritis should undergo a diagnostic workup, based on a careful review of systems, for proper treatment and assessment of prognosis.

Scleritis must be differentiated from both diffuse and nodular episcleritis. Patients with episcleritis do not commonly complain about pain. The eye appears salmon pink to fiery red but not bluish or violaceous and the sclera is not edematous. White diffuse illumination helps detect the depth of the inflammation to differentiate these two disorders. Since the edema and congestion are both localized in superficial episcleral plexus in episcleritis, topically applied 10% phenylephrine blanches the hyperemia, in contrast with scleritis.

Scleral hyaline plaque in elderly people, between the cornea and the insertion of the lateral or medial rectus muscles sometimes can simulate necrotizing scleritis without inflammation. But unlike the findings in scleromalacia perforans the overlying conjunctiva is healthy in these cases.

Posterior scleritis must be differentiated from uveal effusion syndrome, Vogt–Koyanagi–Harada disease and central serous retinopathy. Choroidal melanoma, uveal metastatic tumors, and choroidal hemangioma must be excluded when the patient appears to have a subretinal mass. CT and MRI scans are especially important in these cases.

Systemic vasculitides are the main entities to be considered in the differential diagnosis of scleritis. Therefore, all patients with scleritis should be evaluated carefully for a vasculitic process. Wegener’s granulomatosis is the most common of these and appears to be the underlying etiology in approximately half of cases of vasculitis-associated scleritis. Anti-

neutrophil cytoplasmic antibody (ANCA) (cytoplasmic: c-ANCA and perinuclear: p-ANCA), a circulating autoantibody against intracytoplasmic extranuclear components of neutrophils, is nearly always present in Wegener’s granulamotosis. More importantly, patients with scleritis, positive ANCA results, but no clinical evidence of systemic vasculitis will usually have refractory inflammation, and may need to be treated as for Wegener’s granulamatosis.

TREATMENT

Systemic

The treatment of scleritis always requires systemic therapy based on the type of scleritis, severity of inflammation, and course of the underlying systemic disease. In patients with diffuse or nodular scleritis, oral non-steroidal anti-inflammatory drug (NSAID) therapy (indomethacin sustained-release 75 mg q12h, naproxen sodium 375–500 mg q12h) is the initial choice unless the underlying disease is a known vasculitic disorder. Response to therapy may not be seen until up to 2–3 weeks after commencement of NSAIDs. If the first NSAID is found to be ineffective, another can be tried, up to a maximum of three. Generally patients require a one-year course of therapy before attempting to taper and discontinue the medication. For unresponsive cases and posterior scleritis, oral steroids (prednisone 1 mg/kg/day, up to 60 mg total daily dose) should be considered. With the improvement of clinical findings, the dose can be tapered gradually and the therapy discontinued while maintaining remission with NSAIDs.

Intravenous pulse corticosteroid therapy (methylprednisolone, 1 g/day for 3 consecutive days) followed by oral steroids can be used for refractory cases. Adjunctive preseptal, periorbital and subconjunctival long-acting steroid injections (such as triamcinolone acetonide) have also been reported to be effective in small case series on patients with non-necrotizing scleritis. However, extreme caution should be exercised with these injections as progression to necrosis and perforation can occur. In cases of therapeutic failure of steroids, immunomodulatory drugs such as oral methotrexate (7.5–25 mg once a week), mycophenolate mofetil (1 g/twice daily), azathioprine (2–3 mg/ kg/day), cyclosporin A (2.5–5 mg/kg/day) or cyclophosphamide (2–3 mg/kg/day), may be considered as third-line therapy. Oral corticosteroids should be combined with immunosuppressives during the first 3–4 weeks of the treatment as the response to immunosuppressive therapy may take up to 6 weeks. After the first month of treatment steroids should be tapered slowly and discontinued.

Immunosuppressive therapy as initial treatment is required for definitively diagnosed systemic vasculitic disease, necrotizing scleritis, and/or progressive destructive ocular inflammation especially involving the cornea. Cyclophosphamide is the first choice in these patients and may be given as a single daily oral dose (2–3 mg/kg/day) or as intravenous pulse therapy (750 mg/m² of body surface) in patients with vision threatening conditions. In cases of therapeutic failure, plasmapheresis may be considered.

Although clinicians’ experience is limited as yet, the recent introduction of new immunomodulatory agents has expanded the treatment options, particularly for refractory cases. Daclizumab (1 mg/kg IV) is a newly introduced monoclonal antibody that exerts its effect by binding to the alpha subunit (CD25) of the human interleukin (IL)-2 receptor on the surface of activated lymphocytes, thus preventing the binding of IL-2.

347 CHAPTER Scleritis •