Fig. 4.9 Slit-lamp photomicrograph illustrating the presence of a true scleral nodule in a patient with nodular scleritis. This patientÕs initial presentation was with diffuse anterior scleritis

Although many of the patients initially diagnosed with diffuse scleritis maintain this category throughout the course of their scleral inßammation, attention must be paid to the possibility of progression to another clinical category during subsequent exacerbations of the disease (Fig. 4.9). Of 30 patients with recurrent diffuse scleritis analyzed by Tuft and Watson [13], 12 patients progressed from the diffuse to the nodular variety and 3 patients from the diffuse to the necrotizing variety.

Although permanent loss of visual acuity secondary to keratitis, uveitis, glaucoma, cataract, and macular edema may be present in diffuse anterior scleritis, it is always less severe than in the necrotizing variety. Similarly, although associated diseases may be found in diffuse anterior scleritis, the incidence is smaller than in the necrotizing subcategories. In our series of patients, decrease in vision was recorded in 14% of the patients with diffuse anterior scleritis (Table 4.4). Disease association was found in 36% of the patients with diffuse anterior scleritis; the connective tissue diseases, especially rheumatoid arthritis, were the most common diagnoses (Table 4.5). Patients with diffuse anterior scleritis and connective tissue diseases may progress to necrotizing anterior scleritis if a vasculitic process appears during the course of the connective tissue disease; therefore, the presence of avascular areas in patients with diffuse ante-

rior scleritis must be looked for during a careful follow-up (Fig. 4.10). The Þnding of a diffuse anterior scleritis in association with a connective tissue disease requires an early and adequate treatment of the ocular and systemic diseases to avoid the development of a vasculitic process.

The ßuorescein angiogram usually shows a rapid although structurally normal ßow pattern, with a decreased transit time for the dye; however, in some patients, the ßow pattern is distorted, with the appearance of abnormal anastomoses between the larger vessels in the superÞcial or deep episcleral networks, which may show rapid early leakage (Fig. 4.11). These anastomoses may persist and remain permeable for a prolonged period, even though the eye is uninßamed.

4.2.4.2 Nodular Anterior Scleritis

The inßammation of nodular anterior scleritis is localized to a scleral nodule (or nodules) which is immobile and Þrm to the touch (Fig. 4.12). Signs and symptoms gradually reach a peak in 5Ð10 days, and without treatment they may last for several months. Although it can be misdiagnosed as nodular episcleritis, detailed slit-lamp examination reveals the congestion and tortuosity of the superÞcial and deep episcleral plexuses overlying the nodule. The nodule has a violaceous color due to the vascular congestion and has abnormal anastomosis due to the bypass from the arterial channels to the venous channels. It is usually localized in the interpalpebral region close to the limbus. When the inßammation disappears, the sclera involved may show a bluish color due to the increased translucency secondary to the rearrangement of the collagen Þbers, without scleral thinning or loss of tissue. Sometimes, a mild depression remains in the area where the nodule was.

Although many of the patients initially diagnosed with nodular scleritis maintain this category throughout the course of their scleral inßammation, they must be carefully watched for the possibility of progression to another clinical category during subsequent exacerbations of the disease. Of 54 patients with recurrent nodular scleritis analyzed by Tuft and Watson [13], 10

Fig. 4.10 Presence of avascular area in a patient with previous diffuse anterior scleritis. This area ultimately ÒmeltedÓ leading to scleral thinning and uveal ÒshowÓ characteristic of necrotizing scleritis

Fig. 4.12 Nodular scleritis. This nodule is incorporated into sclera, indeed, is part of the sclera and, therefore, is immobile as one tries to palpate and move it

Fig. 4.11 Anterior segment ßuorescein angiography: early venous phase. Note the leakage of ßuorescein dye as well as the two areas of relative capillary nonprofusion

patients progressed from the nodular to the necrotizing variety and 2 patients from the nodular to the diffuse variety.

The incidence of patients with either decrease in vision or associated diseases is always smaller in those with nodular anterior scleritis than in those with necrotizing anterior scleritis with inßammation. In our series of patients (Table 4.4), decrease in vision was recorded in 11% of the patients with nodular anterior

scleritis. Disease association was found in 30% of the patients with nodular anterior scleritis; the most common diagnoses were of the connective tissue diseases, especially rheumatoid arthritis (Table 4.5). Patients with nodular anterior scleritis and connective tissue diseases may progress to necrotizing anterior scleritis if a vasculitic process appears during the course of the connective tissue disease. The main changes that indicate the development of a necrotizing process are the presence of avascular areas in the nodule or nodules (Fig. 4.13), which can separate from the remaining sclera (leaving the underlying choroid bare or covered only by a thin layer of conjunctiva), and the progression of the nodular scleritis around the circumference of the globe. The Þnding of a nodular anterior scleritis in association with a connective tissue disease requires an early and adequate treatment of the ocular and systemic disease to avoid the development of a vasculitic process.

The ßuorescein angiogram is similar to that of diffuse anterior scleritis. It shows a rapid although structurally normal ßow pattern, although in some patients the ßow pattern is characterized by the appearance of abnormal anastomotic vascular channels that may persist for a long time, even without inßammation. These anastomoses may show rapid early leakage of the dye.

Fig. 4.13 Nodular scleritis evolving into necrotizing scleritis. The area of scleral necrosis is clearly apparent at the 10Ð11 oÕclock position in the anterior sclera adjacent to the corneoscleral limbus. This is an area of previous nodular scleritis

Fig. 4.14 Necrotizing scleritis. Note not only the loss of sclera, but also the pronounced vascularity in the area

4.2.4.3Necrotizing Anterior Scleritis with Inflammation (Necrotizing

Scleritis)

Necrotizing scleritis is the most severe and destructive form of scleritis, sometimes leading to the loss of the eye from multiple complications, severe pain, or even occasionally perforation of the globe. The onset of redness and pain usually is insidious, gradually increasing over 3Ð4 days, although occasionally it can be more acute, reaching the peak after 2 days. The pain, always present without adequate medication, may be so intense and provoked by minimal touch to the scalp that it sometimes seems out of proportion to the ocular Þndings. It usually worsens at night, keeping the patient awake and leading to severe distress and axiety.

The main characteristic determined by ocular examination is the presence of white avascular areas surrounded by swelling of the sclera and acute congestion of the abnormal vascular episcleral channels (Fig. 4.14). The damaged sclera becomes translucent and shows the brown color of the underlying choroid. The inßammation may start in one small patch and remain there with no spreading; without adequate treatment, the inßammation leaves an area of avascular necrotic sclera or sequestrum, which may slough

Fig. 4.15 Necrotizing scleritis. Note the area of full thickness scleral loss with uveal prolapse. This uvea is covered by a thin layer of conjunctival epithelium

away, leaving the choroid covered only by conjunctiva (Fig. 4.15). More frequently, the inßammation starts in one small area that eventually becomes avascular and spreads around the circumference of the globe, often joining other avascular areas that have subsequently appeared (Fig. 4.16), until the whole anterior segment becomes involved. The progression around the globe, leading to loss of tissue, may appear within a few weeks if the inßammation is severe or within several months if the inßammation is moderate. The choroid usually does not protrude through the necrotic areas unless the intraocular pressure rises, but spontaneous or accidental

Fig. 4.16 Necrotizing scleritis. Note that even the conjunctival covering in this patient has broken down, leaving necrotic sclera and uvea exposed

Fig. 4.17 Scleral allograft in a patient with scleral perforation secondary to progressive necrotizing scleritis

perforation may occasionally occur. If the defect is small, replacement by thin Þbrous tissue may occur, but if the defect is large scleral allograft should be performed to maintain the integrity of the globe (Fig. 4.17); scleral grafting must always be associated with systemic immunosuppressive therapy, which may halt the progression of the destructive process [44].

Extension of the inßammatory process may cause keratitis, uveitis, glaucoma, cataract, and macular edema, which may lead to decrease in vision. Fifty percent of our patients with necrotizing anterior scleritis had decrease in vision (Table 4.4).

Necrotizing scleritis is not only a destructive ocular disease; its presence is also considered an ominous sign of potentially lethal systemic vasculitic disease. Watson and Hayreh [2] reported that 29% of the patients with necrotizing scleritis died within Þve years of the onset of the scleritis; many of these deaths were caused by systemic vasculitic lesions. In another study performed by Foster et al. [45], seven of 20 patients with necrotizing scleritis died within eight years of the onset of the scleritis; none of the seven patients had been treated with immunosuppressive therapy. Many of these deaths had been caused by vascu- lar-related events. Eleven of the 13 patients who remained alive had received immunosuppressive therapy. The presence of a necrotizing scleritis may coincide with the onset of vasculitic lesions in a patient with an already known connective tissue disease that is apparently in remission, worsening considerably the ocular and systemic prognoses. A clear example is necrotizing scleritis appearing at the time when systemic vasculitis complicates rheumatoid arthritis. These rheumatoid patients have more destructive joint disease, rheumatoid subcutaneous nodules, cutaneous vascular lesions, more elevated levels of circulating immune complexes, higher titers of rheumatoid factor, more profound hypocomplementemia, and immunoglobulin and complement deposition in vessels of perineural tissue, rheumatoid nodules, synovium, skin, and conjunctiva and/or sclera [18, 46Ð55]. Necrotizing scleritis also may appear during the course of a systemic vasculitic disease, such as polyarteritis nodosa or granulomatosis with polyangiitis (Wegener), demonstrating further evidence of the severity of the disease. Interestingly, necrotizing scleritis may be the Þrst manifestation whose study leads to the diagnosis of a vasculitic disease. Necrotizing scleritis also may be a manifestation of an infectious process that destroys the sclera either through direct microbial damage or an autoimmune process. In our series (Table 4.4), 80% of patients with necrotizing scleritis had an associated disease; of those in whom an etiology was found, 47% had a systemic connective tissue and/ or vasculitic disease and 53% had an infectious

Fig. 4.18 Necrotizing scleritis and peripheral ulcerative keratitis in a patient with positive antineutrophil cytoplasmic antibody staining and abnormal sinus X rays; Granulomatosis with polyangiitis (Weg)

Fig. 4.19 Same patient as in Fig. 4.18, 4 weeks into therapy with systemic cyclophosphamide. The inßammatory process is beginning to resolve

disease (Table 4.5). The most common systemic connective tissue and/or vasculitic diseases were granulomatosis with polyangiitis (Wegener), relapsing polychondritis, rheumatoid arthritis, and arthritis and inßammatory bowel disease. Necrotizing scleritis was the manifestation whose diagnostic study led to the discovery of a noninfectious associated disease in 20% of the patients.

The Þnding of an avascular area either at some point during the course of a recurrent diffuse or nodular scleritis or during an initial presentation of a scleritis is a highly signiÞcant indication of the presence of a necrotizing scleritis. Early treatment of the ocular condition may prevent the extension of the necrotic process before further tissue loss occurs and intraocular complications appear (Figs. 4.18 and 4.19). Early treatment of the associated disease may prevent the extension of the vasculitic process before systemic complications appear.

The ßuorescein angiogram in necrotizing scleritis shows hypoperfusion in the venous site of the capillary network, which may lead to nonperfusion if the venules become thrombosed and permanently occluded (Fig. 4.20). Because these venules rarely open, they are replaced by newly formed vessels that produce persistent leakage. Unlike in episcleritis and diffuse or nodular anterior scleritis, the transit time of the dye in necro-

Fig. 4.20 Anterior segment ßuorescein angiogram of a patient with necrotizing scleritis affecting the temporal hemisphere of the sclera. Note the vast expanse of avascularity

tizing scleritis is markedly increased even when the eye is congested. If the inßammation is severe, vaso-occlusive changes in the conjunctival vessels also may occur.

4.2.4.4Necrotizing Anterior Scleritis Without Inflammation

(Scleromalacia Perforans)

Scleromalacia perforans, a term coined by van der Hoeve in 1931 [56], is characterized by the appearance of yellow or grayish anterior scleral