Once again, the Þeld of neuroendocrine immunology may potentially provide logical explanations for such an association [39]. No clear association between the onset of episcleritis and menstruation or ovulation was evident in any of our female patients.

Exposure to airborne allergens, occupational (e.g., vapor of printing inks), seasonal (e.g., pollen), or perennial (e.g., house dust mite), has also been found to trigger recurrent attacks, as in the case of the patient who had active episcleritis after contact with printerÕs inks [3, 18, 21]. Although several of our patients had positive skin tests to multiple allergens, only one (1%) (Table 4.3) had a clear history of atopy with allergic asthma, hay fever, perennial allergic rhinitis, or atopic dermatitis (eczema). Skin testing was investigated by McGavin et al. [18] in 17 patients with episcleritis. Of the eight patients who had a positive reaction to some allergen (three with mild reaction to one antigen, usually house dust or house dust mite), only three of them gave a clear history of either hay fever or asthma. Twelve percent of the patients with episcleritis in Watson and HayrehÕs series [2] had a history of asthma and hay fever. Allergy to food products has also been reported as a potential trigger of active episcleritis; recurrent attacks or stable periods have been described, depending on the ingestion or avoidance of the speciÞc products in the diet [40Ð42]. None of our patients had a clear association between the onset of the disease and the ingestion of speciÞc food products, but this area of dietary allergy has been an especially difÞcult one to study, historically and experimentally, and so we cannot exclude the possibility that sensitivity to one or another products consumed by some of our patients might be a provocative factor for recurrent episcleritis.

4.2Scleritis

4.2.1Introduction

Unlike episcleritis, scleritis is a severe inßammatory condition that is characterized by edema and inßammatory cell inÞltration of the sclera.

Without treatment, the condition may be progressively destructive, sometimes leading to loss of vision or loss of the eye. Furthermore, scleritis may be the presenting manifestation of a potentially lethal systemic vasculitic disorder or may herald the onset of an occult systemic vasculitis in a patient with an already diagnosed systemic disease that is apparently in remission. Because medical intervention can halt the relentless progression of both ocular and systemic destructive processes, early detection may not only prevent devastating ocular complications, but also may prolong survival and improve the quality of life.

4.2.2Patient Characteristics

Scleritis is most common in the fourth to sixth decades of life, with a peak incidence in the Þfth decade [5, 13, 18], and affects women more frequently than men (1.6:1) [5]. In our series of patients (Table 4.4), the condition had a mean age at the onset of the Þrst episode of 54 years (range, 12Ð96 years) and it was 50% more common among women than men. Our experience shows that scleritis may occur in patients of all races, but there are no studies on its incidence and prevalence within racial groups. Scleritis is not a familial condition, although some of the scleritis-associated systemic diseases (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, reactive arthritis syndrome, BehcetÕs disease, gout, and atopy) have a genetic basis.

4.2.3Clinical Manifestations

Scleritis, like episcleritis, is characterized by recurrences involving the same or different eyes at different times, or both eyes at the same time. Recurrences may appear for many years, especially if the initial attack has not been successfully treated. More than 69% of patients may have recurrences for 3Ð6 years after the onset of the disease; however, after this period, the episodes become less frequent until the disease no longer

recurs [2, 3]. In our series of patients with scleritis, the duration of the disease ranged from 1 month to 30 years. The condition was bilateral in 41% of our patients (Table 4.4). The symptoms and signs of scleritis, when present, are much more severe than in episcleritis. Pain is the main symptom of scleral disease, although it is sometimes almost absent in some patients with posterior scleritis or with scleromalacia perforans. It may be insidious in the onset, severe in intensity, penetrating in character, and only temporarily relieved by analgesics. The pain is sometimes localized to the eye, but it more frequently radiates to the forehead, the jaw, and the sinuses. In these cases, the patient may be erroneously diagnosed as having migraine, temporomandibular joint arthritis, sinusitis, herpes zoster, or orbital tumor. Although the pain may always be present, it can recrudesce with violent paroxysms, sometimes triggered by touching the temple or the eye, preventing the patient from laying his/her head on the affected side. These paroxysms may occur more frequently at night, causing anxiety, depression, and lack of sleep. The pain is probably caused either by distention or destruction of the sensory nerve Þbers in the sclera

as a result of edema, inßammatory mediators, or necrosis [3]. Pain is, therefore, a good indicator of the presence of active scleritis; it always vanishes with adequate medical treatment of the inßammatory condition.

The primary sign of scleritis is redness, which is gradual in the onset, increasing over a period of several days. This redness has a bluish-red tinge in appearance, best seen when the examination is performed in natural light (Fig. 4.4). Redness is present in almost all eyes with scleritis. It may be localized to one sector, most frequently in the interpalpebral area (followed by the superior quadrants) [18] or may involve the whole sclera. After recurrent attacks of scleral inßammation, the sclera becomes translucent due to postedema rearrangement of the collagen Þbers; because the underlying choroidal pigment becomes visible, the translucent sclera shows a blueÐgray color best seen when viewed in daylight (Fig. 4.5). These areas may be invisible by the slit-lamp examination.

Other symptoms include tearing (which is rarely severe and never accompanied by discharge), and mild-to-moderate photophobia. If

Fig. 4.4 Scleritis. Note the slightly violaceous character of the inßammation. The patient complains of pain, and the globe is tender to palpation through the upper lid

Fig. 4.5 Same eye as in Fig. 4.4. Two years after the photograph in Fig. 4.4 was taken. The scleritis has been successfully treated and has been held in remission for 1 year. Note, however, the areas of scleral loss with uveal ÒshowÓ through the remaining scleral Þbers

Fig. 4.6 Patient with necrotizing scleritis prior to instillation of 10% phenylephrine

Fig. 4.7 Same eye as in Fig. 4.6. Ten minutes after instillation of 10% phenylephrine drops. Note that the degree of clinical inßammatory signs is virtually unchanged, indicating that this patientÕs inßammation, even in areas outside the focus of frank necrotizing scleritis, represents true scleritis

the inßammatory process is severe, an associated spasm of the sphincter of the iris and ciliary muscle may appear, resulting in miosis and temporary myopia.

Clinical examination with the slit lamp, particularly with a red-free light, shows that the inßammation is localized within the scleral and episcleral tissue. The deep edge of the narrow beam of the slit lamp is displaced forward, showing the underlying scleral edema. The superÞcial edge of the narrow beam of the slit lamp also is displaced forward, showing the underlying episcleral edema. The deep episcleral vessels are more

congested than the superÞcial episcleral vessels, without coexisting congestion of the conjunctival network. The use of a topical vasoconstrictor (topical phenylephrine [10%] or epinephrine [1:1,000]) makes the differentiation between episcleritis and scleritis easier because the drug constricts the congested superÞcial episcleral network with minimal effect on the congested deep episcleral network (Figs. 4.6 and 4.7).

Scleritis may cause decrease in vision through the complications it produces. The main causes of decrease in vision in patients with scleritis are keratitis, uveitis, glaucoma, cataract, exudative

retinal detachment, and macular edema. In our series of patients with scleritis, 16% had decrease in vision (deÞned as loss of two or more lines on the Snellen eye chart at the end of the follow-up period or visual acuity of 20/80 or less at presentation) (Table 4.4), revealing the permanent changes in visual acuity, even after treatment. Risk factors for decrease in vision included necrotizing scleritis, posterior scleritis, degree of scleral inßammation >2+ (0Ð4+), ocular complications, mainly anterior uveitis and ocular hypertension, and associated underlying disease, mainly infectious.

Fig. 4.8 Diffuse anterior scleritis. The globe is tender to the touch and the inßammation has affected the entire anterior hemisphere of the sclera

4.2.4Classification

Scleritis can be divided into anterior and posterior forms. Even recognizing than posterior scleritis is underdiagnosed, anterior scleritis is much more frequent [2]. In a series of 30 enucleated eyes with the primary histological diagnosis of scleritis, Fraunfelder and Watson [1] found that anterior scleritis was present histologically in 100% of eyes; 43% of them also had posterior scleritis. None of these eyes in this series was found to be affected by posterior scleritis alone. In our own series of patients, 93% of the patients had an anterior scleritis (Table 4.1). Anterior scleritis may be further classiÞed, depending on clinical appearance, into diffuse, nodular, necrotizing with inßammation (necrotizing), and necrotizing without inßammation (scleromalacia perforans) [2]. This classiÞcation has been shown to be useful because only 8% of Tuft and WatsonÕs patients progressed from one subcategory to another during the course of their scleral inßammation [13]. In our series, diffuse anterior scleritis was the most common subcategory, followed by nodular anterior scleritis, posterior scleritis, necrotizing anterior scleritis, and scleromalacia perforans anterior scleritis (Table 4.1) [2, 13, 43]. Although any of these types can be associated with any disease, they serve as an indicator of severity and, therefore, as a guide to therapy. In our series (Table 4.4), the association between age and type of scleritis showed that the mean age of patients with diffuse anterior scleritis (54.2 years) or

nodular anterior scleritis (51.9 years) was lower than the mean age of patients with necrotizing varieties (66.4 years for necrotizing and 61.1 years for scleromalacia perforans) and that the mean age of patients with posterior scleritis was 43.6 years. The sex distribution within each subcategory always maintained the female predominancy, and bilaterality was more frequently linked with diffuse anterior scleritis, necrotizing anterior scleritis, and posterior scleritis. In our series, decrease in vision, anterior uveitis, PUK, and associated disease were signiÞcantly more frequent in necrotizing scleritis.

4.2.4.1 Diffuse Anterior Scleritis

The inßammation of diffuse anterior scleritis is generalized, involving either some small area or the whole anterior segment (Fig. 4.8). The onset is insidious, gradually increasing in signs and symptoms for 5Ð10 days. Without treatment, it may last several months. It is a form that may be misdiagnosed as simple episcleritis and therefore sometimes is undertreated. In slit-lamp examination, the superÞcial and deep episcleral plexuses are not only congested, but also distorted and tortuous, losing the normal radial pattern of the vessels. When the inßammation disappears, the sclera may show a bluish color due to the rearrangement of the collagen Þbers. This increased translucency is not accompanied by scleral thinning or loss of tissue.